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[PMID]:29384978
[Au] Autor:Nishiwaki S; Sugiura I; Miyata Y; Saito S; Sawa M; Nishida T; Miyamura K; Kuwatsuka Y; Kohno A; Yuge M; Kasai M; Iida H; Kurahashi S; Osaki M; Goto T; Terakura S; Murata M; Nishikawa H; Kiyoi H
[Ad] Endereço:Center for Advanced Medicine and Clinical Research, Nagoya University Hospital, Nagoya.
[Ti] Título:Efficacy and safety of autologous peripheral blood stem cell transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia: A study protocol for a multicenter exploratory prospective study (Auto-Ph17 study).
[So] Source:Medicine (Baltimore);96(52):e9568, 2017 Dec.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: The prognosis of Philadelphia chromosome positive acute lymphoblastic leukemia (Ph + ALL) has been dramatically improved since the introduction of tyrosine kinase inhibitors (TKIs). Although allogeneic hematopoietic cell transplantation (allo-HCT) is a major treatment option, the role of autologous peripheral blood stem cell transplantation (auto-PBSCT) has been reconsidered, especially in patients who achieved early molecular remission. METHODS AND ANALYSIS: This is a multicenter exploratory study for Ph + ALL patients aged between 55 and 70 years who achieved complete molecular remission within 3 cycles of chemotherapy. The target sample size is 5, and the registration period is 2 years. The primary endpoint is Day100- mortality after transplantation, and the secondary endpoints are survival, relapse rate, nonrelapse mortality, and adverse events.This study is divided into 3 phases: peripheral blood stem cell harvest, transplantation, and maintenance. Chemomobilization is performed using a combination of cyclophosphamide (CPM), doxorubicin, vincristine (VCR), and prednisolone (PSL). As a preparative regimen, the LEED regimen is used, which consists of melphalan, CPM, etoposide, and dexamethasone. Twelve cycles of maintenance therapy using a combination of VCR, PSL, and dasatinib are performed.In association with relapse, the minimal residual disease (MRD) of BCR-ABL chimeric gene and T-cell subsets are analyzed both before and after auto-PBSCT. ETHICS AND DISSEMINATION: The protocol was approved by the institutional review board of Nagoya University Hospital and all the participating hospitals. Written informed consent was obtained from all patients before registration, in accordance with the Declaration of Helsinki. Results of the study will be disseminated via publications in peer-reviewed journals. TRIAL REGISTRATION: Trial registration number UMIN000026445.
[Mh] Termos MeSH primário: Transplante de Células-Tronco de Sangue Periférico/mortalidade
Transplante de Células-Tronco de Sangue Periférico/métodos
Cromossomo Filadélfia
Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade
Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia
[Mh] Termos MeSH secundário: Idoso
Progressão da Doença
Feminino
Genes abl/fisiologia
Seres Humanos
Imunossupressores/administração & dosagem
Masculino
Meia-Idade
Transplante de Células-Tronco de Sangue Periférico/efeitos adversos
Estudos Prospectivos
Proteínas Proto-Oncogênicas c-bcr/biossíntese
Projetos de Pesquisa
Análise de Sobrevida
[Pt] Tipo de publicação:JOURNAL ARTICLE; MULTICENTER STUDY
[Nm] Nome de substância:
0 (Immunosuppressive Agents); EC 2.7.11.1 (BCR protein, human); EC 2.7.11.1 (Proto-Oncogene Proteins c-bcr)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180220
[Lr] Data última revisão:
180220
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180201
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000009568


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[PMID]:28752801
[Au] Autor:Szewczuk M; Boguszewska K; Zebrowska M; Balcerczak E; Stasiak M; Swiatkowska M; Blaszczak-Swiatkiewicz K
[Ad] Endereço:1 Department of Applied Pharmacy, Medical University of Lodz, Lodz, Poland.
[Ti] Título:Virus-directed enzyme prodrug therapy and the assessment of the cytotoxic impact of some benzimidazole derivatives.
[So] Source:Tumour Biol;39(7):1010428317713675, 2017 Jul.
[Is] ISSN:1423-0380
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Virus-directed enzyme prodrug therapy is one of the major strategy of increasing cytotoxicity of bioreductive agents. This research intended to examine new selected benzimidazole derivatives as a substrate for nitroreductase, the enzyme involved in nitroreduction which is responsible to the production of cytotoxic metabolites. In this way, the selectivity and strength of cytotoxicity can be raised. The effect of benzimidazoles on virus transfected cells and non-virus transfected cells A549 cell line was established by Annexin V + propidium iodide test, western blot, and polymerase chain reaction analysis of specific pro- and anti-apoptotic proteins in the corresponding gene expression and additionally nitroreductase gene expression. Our results proved the pro-apoptotic properties of all tested compounds in normoxia and hypoxia, especially according to virused A549 cells where the time of exposition was reduced from 48 to 4 h. In this shorten period of time, the strongest activity was shown by N-oxide compounds with nitro-groups. The apoptosis was confirmed by generation of BAX gene and protein and reduction of BCL2 gene and protein.
[Mh] Termos MeSH primário: Benzimidazóis/administração & dosagem
Hipóxia Celular/efeitos dos fármacos
Neoplasias Pulmonares/tratamento farmacológico
Pró-Fármacos/administração & dosagem
[Mh] Termos MeSH secundário: Células A549
Apoptose/efeitos dos fármacos
Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos
Vetores Genéticos/administração & dosagem
Seres Humanos
Neoplasias Pulmonares/patologia
Proteínas Proto-Oncogênicas c-bcr/biossíntese
Transfecção
Proteína X Associada a bcl-2/biossíntese
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Benzimidazoles); 0 (Prodrugs); 0 (bcl-2-Associated X Protein); E24GX49LD8 (benzimidazole); EC 2.7.11.1 (BCR protein, human); EC 2.7.11.1 (Proto-Oncogene Proteins c-bcr)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170815
[Lr] Data última revisão:
170815
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170729
[St] Status:MEDLINE
[do] DOI:10.1177/1010428317713675


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[PMID]:28644972
[Au] Autor:Adem J; Eray M; Eeva J; Nuutinen U; Pelkonen J
[Ad] Endereço:Department of Clinical Microbiology, Institute of Clinical Medicine, University of Eastern Finland, Yliopistonranta 1C, 70210 Kuopio, Finland. Electronic address: jemal.adem@uef.fi.
[Ti] Título:Advantages of targeting B cell receptor complex to treat B-cell derived autoimmune diseases and lymphomas.
[So] Source:Mol Immunol;88:135-137, 2017 Aug.
[Is] ISSN:1872-9142
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Antibodies produced by B-cells provide protection from infectious agents. However, impaired cell death signaling pathways in B-cells can lead to cancer, immunodeficiency or autoimmune diseases. B-cell signaling molecules such as CD20, CD19, Btk, and BAFF-R are targeted by therapeutic drugs and used to treat B-cell derived lymphomas or autoimmune diseases. Nevertheless, B-cells could develop resistance to these therapeutic drugs or the therapeutic drugs may have off-target effects. For instance, repeated rituximab (anti-CD20 antibody) treatment may lead to the loss of its target cell surface molecule, CD20. In addition, in B-cell malignancies, loss of CD19 expression has been observed. Another target molecule, Btk is expressed not only in B-cells but also in mast cells, macrophages, and dendritic cells. Thus, targeting Btk could negatively regulate the functions of innate immunity. The expression of BAFF-R is thought to be restricted to B-cells but it is also expressed on T-cells. Targeting BAFF-R, therefore, may lead to depletion of T-cells in addition to B-cells. B cell receptor (BCR) expression and signaling, however, are critically important for development, differentiation and survival of B-cells. Moreover, BCR is exclusively expressed on B-cells, which makes it an excellent target to avoid off-target effects.
[Mh] Termos MeSH primário: Antígenos CD19/metabolismo
Antígenos CD20/metabolismo
Doenças Autoimunes/tratamento farmacológico
Linfócitos B/imunologia
Linfoma de Células B/tratamento farmacológico
Proteínas Proto-Oncogênicas c-bcr/metabolismo
Rituximab/uso terapêutico
[Mh] Termos MeSH secundário: Doenças Autoimunes/patologia
Receptor do Fator Ativador de Células B/metabolismo
Resistência a Medicamentos Antineoplásicos
Seres Humanos
Linfoma de Células B/patologia
Proteínas Tirosina Quinases/metabolismo
[Pt] Tipo de publicação:LETTER
[Nm] Nome de substância:
0 (Antigens, CD19); 0 (Antigens, CD20); 0 (B-Cell Activation Factor Receptor); 0 (TNFRSF13C protein, human); 4F4X42SYQ6 (Rituximab); EC 2.7.10.1 (Agammaglobulinaemia tyrosine kinase); EC 2.7.10.1 (Protein-Tyrosine Kinases); EC 2.7.11.1 (BCR protein, human); EC 2.7.11.1 (Proto-Oncogene Proteins c-bcr)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171009
[Lr] Data última revisão:
171009
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170624
[St] Status:MEDLINE


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[PMID]:28573218
[Au] Autor:Sangkaruk R; Rungrojsakul M; Tima S; Anuchapreeda S
[Ad] Endereço:Division of Clinical Microscopy, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200 Thailand.
[Ti] Título:EFFECT OF THAI SARAPHI FLOWER EXTRACTS ON WT1 AND BCR/ABL PROTEIN EXPRESSION IN LEUKEMIC CELL LINES.
[So] Source:Afr J Tradit Complement Altern Med;14(2):16-24, 2017.
[Is] ISSN:2505-0044
[Cp] País de publicação:Nigeria
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Saraphi is a Thai traditional herb. In this study, the cytotoxic effects of crude ethanolic and fractional extracts including hexane, ethyl acetate, and methanol fractions from flowers were investigated in order to determine their effect on WT1 expression in Molt4 and K562 cells and Bcr/Abl expression in K562 cells. MATERIALS AND METHODS: The flowers of were extracted using ethanol. The ethanol flower extract was further fractionated with hexane, ethyl acetate, and methanol. Cytotoxic effects were measured by the MTT assay. Bcr/Abl and WT1 protein levels after treatments were determined by Western blotting. The total cell number was determined the typan blue exclusion method. RESULTS: The hexane fraction showed the strongest cytotoxic activity on Molt4 and K562 cells, with IC values of 2.6 and 77.6 µg/ml, respectively. The hexane extract decreased Bcr/Abl protein expression in K562 cells by 74.6% and WT1 protein expressions in Molt4 and K562 cells by 68.4 and 72.1%, respectively. Total cell numbers were decreased by 66.2 and 48.7% in Molt4 and K562 cells, respectively. Mammea E/BB (main active compound) significantly decreased both Bcr/Abl and WTlprotein expressions by 75 and 49.5%, respectively when compared to vehicle control. CONCLUSION: The hexane fraction from flowers inhibited cell proliferation the suppression of WT1 expression in Molt4 and K562 cells and Bcr/Abl expression in K562 cells. The active compound may be mammea E/BB. Extracts from flowers show promise as naturally occurring anti-cancer drugs.
[Mh] Termos MeSH primário: Antineoplásicos Fitogênicos/uso terapêutico
Proteínas de Fusão bcr-abl/metabolismo
Leucemia/tratamento farmacológico
Mammea
Fitoterapia
Extratos Vegetais/uso terapêutico
Proteínas WT1/metabolismo
[Mh] Termos MeSH secundário: Antineoplásicos Fitogênicos/farmacologia
Proliferação Celular
Flores
Seres Humanos
Células K562
Leucemia/metabolismo
Medicina Tradicional
Proteínas Oncogênicas v-abl/metabolismo
Extratos Vegetais/farmacologia
Proteínas Proto-Oncogênicas c-bcr/metabolismo
Tailândia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents, Phytogenic); 0 (Oncogene Proteins v-abl); 0 (Plant Extracts); 0 (WT1 Proteins); 0 (WT1 protein, human); 0 (abl-bcr fusion protein, human); EC 2.7.10.2 (Fusion Proteins, bcr-abl); EC 2.7.11.1 (BCR protein, human); EC 2.7.11.1 (Proto-Oncogene Proteins c-bcr)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170816
[Lr] Data última revisão:
170816
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170603
[St] Status:MEDLINE
[do] DOI:10.21010/ajtcam.v14i2.3


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[PMID]:28551329
[Au] Autor:Montenegro-Garreaud X; Miranda RN; Reynolds A; Tang G; Wang SA; Yabe M; Wang W; Fang L; Bueso-Ramos CE; Lin P; Medeiros LJ; Lu X
[Ad] Endereço:Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Clinical Genetics, Instituto Nacional de Enfermedades Neoplasicas and Universidad Peruana Cayetano Heredia, Lima, Peru.
[Ti] Título:Myeloproliferative neoplasms with t(8;22)(p11.2;q11.2)/BCR-FGFR1: a meta-analysis of 20 cases shows cytogenetic progression with B-lymphoid blast phase.
[So] Source:Hum Pathol;65:147-156, 2017 Jul.
[Is] ISSN:1532-8392
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Rearrangements of FGFR1 result in the 8p11 myeloproliferative syndrome, a group of rare diseases that features a myeloproliferative neoplasm (MPN) that commonly progresses to lymphoblastic leukemia/lymphoma or acute myeloid leukemia. The most common partner of FGFR1 is ZMYM2, and patients with the ZMYM2-FGFR1 fusion often present with MPN and T-lymphoblastic lymphoma. There are 14 other partners that can fuse with FGFR1, and of interest is the BCR-FGFR1 fusion that results from t(8;22)(p11.2;q11.2). Patients with t(8;22) often show leukocytosis and present with an MPN resembling chronic myeloid leukemia or very rarely, with B-lymphoblastic leukemia (B-ALL). In this study, we analyzed the clinicopathological, cytogenetic, and molecular features of 2 new patients with the t(8;22)(p11.2;q11.2)/BCR-FGFR1 who presented with B-ALL. An underlying MPN became apparent when a morphologic remission of B-ALL was achieved after chemotherapy. We subsequently reviewed the literature and identified 18 additional cases reported with B-ALL in a background MPN or with the MPN as a chronic phase. Our data suggest that the t(8;22)(p11.2;q11.2)/BCR-FGFR1 may arise from a myeloid/B progenitor cell. It is important to recognize that neoplasms carrying the t(8;22)/BCR-FGFR1, although rare, can commonly with B lymphoblastic leukemia at the initial diagnosis, which could distract one from recognizing a possible underlying 8p11 myeloproliferative syndrome.
[Mh] Termos MeSH primário: Biomarcadores Tumorais/genética
Cromossomos Humanos Par 22
Cromossomos Humanos Par 8
Análise Citogenética
Transtornos Mieloproliferativos/genética
Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética
Células Precursoras de Linfócitos B/patologia
Translocação Genética
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Antineoplásicos/uso terapêutico
Criança
Bases de Dados Factuais
Diagnóstico Diferencial
Erros de Diagnóstico
Progressão da Doença
Feminino
Fusão Gênica
Predisposição Genética para Doença
Seres Humanos
Hibridização in Situ Fluorescente
Cariotipagem
Masculino
Meia-Idade
Transtornos Mieloproliferativos/tratamento farmacológico
Transtornos Mieloproliferativos/patologia
Fenótipo
Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamento farmacológico
Leucemia-Linfoma Linfoblástico de Células Precursoras B/patologia
Células Precursoras de Linfócitos B/efeitos dos fármacos
Valor Preditivo dos Testes
Proteínas Proto-Oncogênicas c-bcr/genética
Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética
Estudos Retrospectivos
Resultado do Tratamento
Adulto Jovem
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE; META-ANALYSIS; REVIEW
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Biomarkers, Tumor); EC 2.7.10.1 (FGFR1 protein, human); EC 2.7.10.1 (Receptor, Fibroblast Growth Factor, Type 1); EC 2.7.11.1 (BCR protein, human); EC 2.7.11.1 (Proto-Oncogene Proteins c-bcr)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170529
[St] Status:MEDLINE


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[PMID]:28424165
[Au] Autor:Kruth KA; Fang M; Shelton DN; Abu-Halawa O; Mahling R; Yang H; Weissman JS; Loh ML; Müschen M; Tasian SK; Bassik MC; Kampmann M; Pufall MA
[Ad] Endereço:Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City, IA.
[Ti] Título:Suppression of B-cell development genes is key to glucocorticoid efficacy in treatment of acute lymphoblastic leukemia.
[So] Source:Blood;129(22):3000-3008, 2017 Jun 01.
[Is] ISSN:1528-0020
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Glucocorticoids (GCs), including dexamethasone (dex), are a central component of combination chemotherapy for childhood B-cell precursor acute lymphoblastic leukemia (B-ALL). GCs work by activating the GC receptor (GR), a ligand-induced transcription factor, which in turn regulates genes that induce leukemic cell death. Which GR-regulated genes are required for GC cytotoxicity, which pathways affect their regulation, and how resistance arises are not well understood. Here, we systematically integrate the transcriptional response of B-ALL to GCs with a next-generation short hairpin RNA screen to identify GC-regulated "effector" genes that contribute to cell death, as well as genes that affect the sensitivity of B-ALL cells to dex. This analysis reveals a pervasive role for GCs in suppression of B-cell development genes that is linked to therapeutic response. Inhibition of phosphatidylinositol 3-kinase δ (PI3Kδ), a linchpin in the pre-B-cell receptor and interleukin 7 receptor signaling pathways critical to B-cell development (with CAL-101 [idelalisib]), interrupts a double-negative feedback loop, enhancing GC-regulated transcription to synergistically kill even highly resistant B-ALL with diverse genetic backgrounds. This work not only identifies numerous opportunities for enhanced lymphoid-specific combination chemotherapies that have the potential to overcome treatment resistance, but is also a valuable resource for understanding GC biology and the mechanistic details of GR-regulated transcription.
[Mh] Termos MeSH primário: Glucocorticoides/uso terapêutico
Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamento farmacológico
Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética
Células Precursoras de Linfócitos B/efeitos dos fármacos
Células Precursoras de Linfócitos B/patologia
[Mh] Termos MeSH secundário: Morte Celular/efeitos dos fármacos
Morte Celular/genética
Linhagem Celular Tumoral
Classe I de Fosfatidilinositol 3-Quinases/antagonistas & inibidores
Classe I de Fosfatidilinositol 3-Quinases/genética
Classe I de Fosfatidilinositol 3-Quinases/metabolismo
Dexametasona/farmacologia
Resistência a Medicamentos Antineoplásicos/genética
Regulação da Expressão Gênica/efeitos dos fármacos
Seres Humanos
Leucemia-Linfoma Linfoblástico de Células Precursoras B/patologia
Células Precursoras de Linfócitos B/metabolismo
Proteínas Proto-Oncogênicas c-bcr/genética
Proteínas Proto-Oncogênicas c-bcr/metabolismo
RNA Interferente Pequeno/genética
Receptores de Glucocorticoides/efeitos dos fármacos
Transdução de Sinais
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Glucocorticoids); 0 (RNA, Small Interfering); 0 (Receptors, Glucocorticoid); 7S5I7G3JQL (Dexamethasone); EC 2.7.1.137 (Class I Phosphatidylinositol 3-Kinases); EC 2.7.1.137 (PIK3CD protein, human); EC 2.7.11.1 (BCR protein, human); EC 2.7.11.1 (Proto-Oncogene Proteins c-bcr)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171121
[Lr] Data última revisão:
171121
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170421
[St] Status:MEDLINE
[do] DOI:10.1182/blood-2017-02-766204


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[PMID]:28419476
[Au] Autor:Martini V; Gattazzo C; Frezzato F; Trimarco V; Pizzi M; Chiodin G; Severin F; Scomazzon E; Guzzardo V; Saraggi D; Raggi F; Martinello L; Facco M; Visentin A; Piazza F; Brunati AM; Semenzato G; Trentin L
[Ad] Endereço:Department of Medicine, Haematology and Clinical Immunology Branch, Padua University School of Medicine, University of Padova, Padova, Italy.
[Ti] Título:Cortactin, a Lyn substrate, is a checkpoint molecule at the intersection of BCR and CXCR4 signalling pathway in chronic lymphocytic leukaemia cells.
[So] Source:Br J Haematol;178(1):81-93, 2017 Jul.
[Is] ISSN:1365-2141
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Cortactin (CTTN) is a substrate of the Src kinase Lyn that is known to play an actin cytoskeletal regulatory role involved in cell migration and cancer progression following its phosphorylation at Y421. We recently demonstrated that Cortactin is overexpressed in patients with chronic lymphocytic leukaemia (CLL). This work was aimed at defining the functional role of Cortactin in these patients. We found that Cortactin is variably expressed in CLL patients both in the peripheral blood and lymph nodes and that its expression correlates with the release of matrix metalloproteinase 9 (MMP-9) and the motility of neoplastic cells. Cortactin knockdown, by siRNA, induced a reduction in MMP-9 release as well as a decrease of migration capability of leukaemic B cells in vitro, also after chemotactic stimulus. Furthermore, Cortactin phosphorylation was lowered by the Src kinase-inhibitor PP2 with a consequent decrease of MMP-9 release in culture medium. An impaired migration, as compared to control experiments without Cortactin knockdown, was observed following CXCL12 triggering. Reduced Cortactin expression and phosphorylation were also detected both in vivo and in vitro after treatment with Ibrutinib, a Btk inhibitor. Our results highlight the role of Cortactin in CLL as a check-point molecule between the BCR and CXCR4 signalling pathways.
[Mh] Termos MeSH primário: Pontos de Checagem do Ciclo Celular/fisiologia
Cortactina/fisiologia
Leucemia Linfocítica Crônica de Células B/metabolismo
Proteínas Proto-Oncogênicas c-bcr/fisiologia
Receptores CXCR4/fisiologia
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Antineoplásicos/farmacologia
Antineoplásicos/uso terapêutico
Movimento Celular/fisiologia
Feminino
Seres Humanos
Leucemia Linfocítica Crônica de Células B/tratamento farmacológico
Leucemia Linfocítica Crônica de Células B/patologia
Masculino
Metaloproteinase 9 da Matriz/metabolismo
Meia-Idade
Proteínas de Neoplasias/fisiologia
Fosforilação/efeitos dos fármacos
Proteínas Tirosina Quinases/antagonistas & inibidores
Pirazóis/farmacologia
Pirazóis/uso terapêutico
Pirimidinas/farmacologia
Pirimidinas/uso terapêutico
Transdução de Sinais/fisiologia
Células Tumorais Cultivadas
Quinases da Família src/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (CXCR4 protein, human); 0 (Cortactin); 0 (Neoplasm Proteins); 0 (PCI 32765); 0 (Pyrazoles); 0 (Pyrimidines); 0 (Receptors, CXCR4); EC 2.7.10.1 (Agammaglobulinaemia tyrosine kinase); EC 2.7.10.1 (Protein-Tyrosine Kinases); EC 2.7.10.2 (src-Family Kinases); EC 2.7.11.1 (Proto-Oncogene Proteins c-bcr); EC 3.4.24.35 (Matrix Metalloproteinase 9)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170906
[Lr] Data última revisão:
170906
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170419
[St] Status:MEDLINE
[do] DOI:10.1111/bjh.14642


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[PMID]:28408486
[Au] Autor:Karvonen H; Niininen W; Murumägi A; Ungureanu D
[Ad] Endereço:BioMediTech, BMT, University of Tampere, Tampere 33014, Finland.
[Ti] Título:Targeting ROR1 identifies new treatment strategies in hematological cancers.
[So] Source:Biochem Soc Trans;45(2):457-464, 2017 Apr 15.
[Is] ISSN:1470-8752
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is a member of the ROR receptor family consisting of two closely related type I transmembrane proteins ROR1 and ROR2. Owing to mutations in their canonical motifs required for proper kinase activity, RORs are classified as pseudokinases lacking detectable catalytic activity. ROR1 stands out for its selective and high expression in numerous blood and solid malignancies compared with a minimal expression in healthy adult tissues, suggesting high potential for this molecule as a drug target for cancer therapy. Current understanding attributes a survival role for ROR1 in cancer cells; however, its oncogenic function is cancer-type-specific and involves various signaling pathways. High interest in ROR1-targeted therapies resulted in the development of ROR1 monoclonal antibodies such as cirmtuzumab, currently in a phase I clinical trial for chronic lymphocytic leukemia. Despite these advances in translational studies, the molecular mechanism employed by ROR1 in different cancers is not yet fully understood; therefore, more insights into the oncogenic role of ROR1 signaling are crucial in order to optimize the use of targeted drugs. Recent studies provided evidence that targeting ROR1 simultaneously with inhibition of B-cell receptor (BCR) signaling is more effective in killing ROR1-positive leukemia cells, suggesting a synergistic correlation between co-targeting ROR1 and BCR pathways. Although this synergy has been previously reported for B-cell acute lymphoblastic leukemia, the molecular mechanism appears rather different. These results provide more insights into ROR1-BCR combinatorial treatment strategies in hematological malignancies, which could benefit in tailoring more effective targeted therapies in other ROR1-positive cancers.
[Mh] Termos MeSH primário: Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia
Neoplasias Hematológicas/tratamento farmacológico
Terapia de Alvo Molecular/métodos
Proteínas Proto-Oncogênicas c-bcr/antagonistas & inibidores
Receptores Órfãos Semelhantes a Receptor Tirosina Quinase/antagonistas & inibidores
[Mh] Termos MeSH secundário: Animais
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Ensaios Clínicos como Assunto
Sinergismo Farmacológico
Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos
Neoplasias Hematológicas/genética
Neoplasias Hematológicas/metabolismo
Seres Humanos
Receptores Órfãos Semelhantes a Receptor Tirosina Quinase/genética
Receptores Órfãos Semelhantes a Receptor Tirosina Quinase/metabolismo
Transdução de Sinais
Pesquisa Médica Translacional
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
EC 2.7.10.1 (ROR1 protein, human); EC 2.7.10.1 (Receptor Tyrosine Kinase-like Orphan Receptors); EC 2.7.11.1 (BCR protein, human); EC 2.7.11.1 (Proto-Oncogene Proteins c-bcr)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170502
[Lr] Data última revisão:
170502
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170415
[St] Status:MEDLINE
[do] DOI:10.1042/BST20160272


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[PMID]:28125133
[Au] Autor:Zhang X; Yang C; Peng X; Chen X; Feng Y
[Ad] Endereço:MD, PhD. Professor, Department of Hematology, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
[Ti] Título:Acute WT1-positive promyelocytic leukemia with hypogranular variant morphology, bcr-3 isoform of PML-RARα and Flt3-ITD mutation: a rare case report.
[So] Source:Sao Paulo Med J;135(2):179-184, 2017 Mar-Apr.
[Is] ISSN:1806-9460
[Cp] País de publicação:Brazil
[La] Idioma:eng
[Ab] Resumo:CONTEXT:: Acute promyelocytic leukemia (APL) accounts for 8% to 10% of cases of acute myeloid leukemia (AML). Remission in cases of high-risk APL is still difficult to achieve, and relapses occur readily. CASE REPORT:: Here, we describe a case of APL with high white blood cell counts in blood tests and hypogranular variant morphology in bone marrow, together with fms-like tyrosine kinase-3 with internal tandem duplication mutations (FLT3-ITD), and bcr-3 isoform of PML-RARα. Most importantly, we detected high level of Wilms' tumor gene (WT1) in marrow blasts, through the reverse transcription polymerase chain reaction (RT-PCR). To date, no clear conclusions about an association between WT1 expression levels and APL have been reached. This patient successively received a combined treatment regimen consisting of hydroxycarbamide, arsenic trioxide and idarubicin plus cytarabine, which ultimately enabled complete remission. Unfortunately, he subsequently died of sudden massive hemoptysis because of pulmonary infection. CONCLUSION:: Based on our findings and a review of the literature, abnormal functioning of WT1 may be a high-risk factor in cases of APL. Further studies aimed towards evaluating the impact of WT1 expression on the prognosis for APL patients are of interest.
[Mh] Termos MeSH primário: Genes do Tumor de Wilms
Leucemia Promielocítica Aguda/genética
Tirosina Quinase 3 Semelhante a fms/genética
[Mh] Termos MeSH secundário: Adulto
Seres Humanos
Leucemia Promielocítica Aguda/tratamento farmacológico
Leucemia Promielocítica Aguda/patologia
Masculino
Mutação
Reação em Cadeia da Polimerase
Prognóstico
Proteínas Proto-Oncogênicas c-bcr
Fatores de Risco
[Pt] Tipo de publicação:CASE REPORTS
[Nm] Nome de substância:
EC 2.7.10.1 (fms-Like Tyrosine Kinase 3); EC 2.7.11.1 (BCR protein, human); EC 2.7.11.1 (Proto-Oncogene Proteins c-bcr)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171006
[Lr] Data última revisão:
171006
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170127
[St] Status:MEDLINE


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[PMID]:27748288
[Au] Autor:Nandagopalan SR; Kuila N; Biswas S; Pattnayak NC; Biswas G; Chakraborty S
[Ad] Endereço:Institute of Life Sciences, Bhubaneswar, Odisha, India.
[Ti] Título:Dual transcripts of - & different polymorphisms in chronic myeloid leukaemia patients.
[So] Source:Indian J Med Res;143(Supplement):S136-S141, 2016 May.
[Is] ISSN:0971-5916
[Cp] País de publicação:India
[La] Idioma:eng
[Ab] Resumo:BACKGROUND & OBJECTIVES: Chronic myeloid leukaemia is (CML) characterized by the presence of a hallmark chromosomal translocation, the Philadelphia chromosome. Although there are many reports available regarding the different variants of BCR-ABL in CML, we studied the co-expression of e13a2 and e14a2 transcripts and a few polymorphisms in CML patients. METHODS: Molecular genetics approach was adapted to screen for polymorphisms, mutation and translocation in BCR, ABL kinase domain and BCR-ABL breakpoint region in 73 CML patients. RESULTS: All eight patients with dual transcripts were found to harbour an exonic polymorphism (c.2700 T>C) and an intronic polymorphism (g.109366A>G) that were earlier reported to be associated with co-expression of both the transcripts. We also observed c.763G>A mutation in ABL kinase domain and two polymorphisms, c.2387 A>G and c.2736A>G in the BCR gene. INTERPRETATION & CONCLUSIONS: Though our data support the previous findings that co-expression of BCR-ABL transcripts is due to the occurrence of exonic and intronic polymorphisms in the BCR gene, it also shows that the intronic polymorphism can arise without the linked exonic polymorphism. The occurrence of ABL kinase domain mutation is less frequent in Indian population.
[Mh] Termos MeSH primário: Proteínas de Fusão bcr-abl/genética
Leucemia Mielogênica Crônica BCR-ABL Positiva/genética
Proteínas Oncogênicas v-abl/genética
Proteínas Proto-Oncogênicas c-bcr/genética
Translocação Genética/genética
[Mh] Termos MeSH secundário: Adulto
Éxons/genética
Feminino
Seres Humanos
Índia
Íntrons/genética
Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia
Masculino
Meia-Idade
Mutação
Cromossomo Filadélfia
Polimorfismo Genético
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Oncogene Proteins v-abl); EC 2.7.10.2 (Fusion Proteins, bcr-abl); EC 2.7.11.1 (BCR protein, human); EC 2.7.11.1 (Proto-Oncogene Proteins c-bcr)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170817
[Lr] Data última revisão:
170817
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161018
[St] Status:MEDLINE
[do] DOI:10.4103/0971-5916.191816



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