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[PMID]:29392424
[Au] Autor:Shahkarami S; Mehrasa R; Younesian S; Yaghmaie M; Chahardouli B; Vaezi M; Rezaei N; Nikbakht M; Alimoghaddam K; Ghavamzadeh A; Tavakkoly-Bazzaz J; Ghaffari SH
[Ad] Endereço:Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
[Ti] Título:Minimal residual disease (MRD) detection using rearrangement of immunoglobulin/T cell receptor genes in adult patients with acute lymphoblastic leukemia (ALL).
[So] Source:Ann Hematol;97(4):585-595, 2018 Apr.
[Is] ISSN:1432-0584
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:MRD detection with allele-specific oligonucleotide-quantitative polymerase chain reaction (ASO-qPCR) and using clone-specific immunoglobulin/T cell receptor rearrangements is considered as a powerful prognostic factor in acute lymphoblastic leukemia (ALL). In the present study, we evaluated an ASO-qPCR assay for MRD quantification in peripheral blood (PB) samples of adult patients with ALL. DNA was isolated from PB samples of patients with newly diagnosed ALL. They were first investigated by multiplex-PCR assay to identify V/J usage. An ASO-qPCR technique was then applied for 2.5-year monthly MRD quantification for detection of patient-specific Ig/TCR receptor rearrangements as a molecular target. From 98 patients who were diagnosed as ALL, 72 (73.5%) were enrolled in the present study for MRD detection. MRD was successfully quantified in patients with 1-month interval time. MRD level at the end of induction therapy up to day 88 was the only significant prognostic factor. Regarding MRD level, patients were categorized into two groups of low and high-risk. 2.5-year OS in all three time points (days 28, 58 and 88) were significantly lower in high-risk group (P < 0.008). The results of the 2.5-year MRD detection indicate that MRD level at the end of induction up to about 6 months after the first diagnosis was associated with clinical outcome. This study may highlight the usefulness of PB and the definitions of cut-off level for early prediction of relapse and for stratifying ALL patients. Short-interval time points and frequent PB sampling to monitor MRD level is suggested for early clinical relapse prediction and clinical management of the disease.
[Mh] Termos MeSH primário: Rearranjo Gênico do Linfócito T/efeitos dos fármacos
Quimioterapia de Indução
Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico
[Mh] Termos MeSH secundário: Adulto
Alelos
Feminino
Seguimentos
Hospitais Universitários
Seres Humanos
Irã (Geográfico)
Masculino
Reação em Cadeia da Polimerase Multiplex
Proteínas de Neoplasias/química
Proteínas de Neoplasias/genética
Proteínas de Neoplasias/metabolismo
Neoplasia Residual/diagnóstico
Neoplasia Residual/genética
Neoplasia Residual/metabolismo
Neoplasia Residual/patologia
Oligonucleotídeos/química
Oligonucleotídeos/metabolismo
Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico
Leucemia-Linfoma Linfoblástico de Células Precursoras/genética
Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia
Prognóstico
Estudos Prospectivos
Reação em Cadeia da Polimerase em Tempo Real
Reação em Cadeia da Polimerase Via Transcriptase Reversa
Medição de Risco
Análise de Sobrevida
Carga Tumoral/efeitos dos fármacos
[Pt] Tipo de publicação:EVALUATION STUDIES; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Neoplasm Proteins); 0 (Oligonucleotides)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180203
[St] Status:MEDLINE
[do] DOI:10.1007/s00277-018-3230-z


  2 / 22574 MEDLINE  
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[PMID]:29348612
[Au] Autor:Wiemels JL; Walsh KM; de Smith AJ; Metayer C; Gonseth S; Hansen HM; Francis SS; Ojha J; Smirnov I; Barcellos L; Xiao X; Morimoto L; McKean-Cowdin R; Wang R; Yu H; Hoh J; DeWan AT; Ma X
[Ad] Endereço:Department of Epidemiology and Biostatistics, University of California San Francisco, 1450 3rd Street, San Francisco, CA, 94158, USA. joe.wiemels@ucsf.edu.
[Ti] Título:GWAS in childhood acute lymphoblastic leukemia reveals novel genetic associations at chromosomes 17q12 and 8q24.21.
[So] Source:Nat Commun;9(1):286, 2018 01 18.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Childhood acute lymphoblastic leukemia (ALL) (age 0-14 years) is 20% more common in Latino Americans than non-Latino whites. We conduct a genome-wide association study in a large sample of 3263 Californian children with ALL (including 1949 of Latino heritage) and 3506 controls matched on month and year of birth, sex, and ethnicity, and an additional 12,471 controls from the Kaiser Resource for Genetic Epidemiology Research on Aging Cohort. Replication of the strongest genetic associations is performed in two independent datasets from the Children's Oncology Group and the California Childhood Leukemia Study. Here we identify new risk loci on 17q12 near IKZF3/ZPBP2/GSDMB/ORMDL3, a locus encompassing a transcription factor important for lymphocyte development (IKZF3), and at an 8q24 region known for structural contacts with the MYC oncogene. These new risk loci may impact gene expression via local (four 17q12 genes) or long-range (8q24) interactions, affecting function of well-characterized hematopoietic and growth-regulation pathways.
[Mh] Termos MeSH primário: Cromossomos Humanos Par 17/genética
Cromossomos Humanos Par 8/genética
Predisposição Genética para Doença/genética
Estudo de Associação Genômica Ampla
Leucemia-Linfoma Linfoblástico de Células Precursoras/genética
[Mh] Termos MeSH secundário: Adolescente
California
Pré-Escolar
Feminino
Frequência do Gene
Predisposição Genética para Doença/etnologia
Hispano-Americanos/genética
Seres Humanos
Lactente
Recém-Nascido
Masculino
Polimorfismo de Nucleotídeo Único
Leucemia-Linfoma Linfoblástico de Células Precursoras/etnologia
Fatores de Risco
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[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:180120
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02596-9


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[PMID]:29237521
[Au] Autor:Zhang PF; Feng XQ; Wu CL; Zhang YM
[Ad] Endereço:Department of Pediatrics, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. yumingzhang1966@hotmail.com.
[Ti] Título:[Clinical features of children with acute lymphoblastic leukemia complicated by pulmonary infection after chemotherapy].
[So] Source:Zhongguo Dang Dai Er Ke Za Zhi;19(12):1234-1238, 2017 Dec.
[Is] ISSN:1008-8830
[Cp] País de publicação:China
[La] Idioma:chi
[Ab] Resumo:OBJECTIVE: To examine the clinical features of children with acute lymphoblastic leukemia (ALL) complicated by pulmonary infection after chemotherapy. METHODS: The clinical data of 108 ALL children (115 case-times) with post-chemotherapy pulmonary infection were retrospectively reviewed. The risk factors for pulmonary infection and the relationship between pathogens and chest CT findings were evaluated. RESULTS: The highest incidence (77.4% ) of pulmonary infection occurred during remission induction, peaking at 31-60 days after chemotherapy. Patients with neutropenia had the highest incidence rate of pulmonary infection (67.0%). Bacteria (36%) and fungi (41%) were the two most common pathogens in the 41 patients who were etiologically suspected of or diagnosed with pulmonary infection. There was no significant difference in chest CT findings between patients with bacterial and fungal infections. CONCLUSIONS: The children with ALL are most susceptible to pulmonary infection during remission induction, especially when they are neutropenic. Bacteria and fungi are the main pathogens of pulmonary infections in these patients. However, the changes in chest CT images are poor indicators of the nature of pulmonary infection.
[Mh] Termos MeSH primário: Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico
Infecções Respiratórias/etiologia
[Mh] Termos MeSH secundário: Adolescente
Criança
Pré-Escolar
Feminino
Seres Humanos
Lactente
Masculino
Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações
Infecções Respiratórias/diagnóstico por imagem
Infecções Respiratórias/epidemiologia
Infecções Respiratórias/microbiologia
Estudos Retrospectivos
Tomografia Computadorizada por Raios X
[Pt] Tipo de publicação:JOURNAL ARTICLE
[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:171215
[St] Status:MEDLINE


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[PMID]:29187149
[Au] Autor:Meng Q; Catchpoole D; Skillicorn D; Kennedy PJ
[Ad] Endereço:School of Software, Faculty of Engineering and Information Technology and the Centre for Artificial Intelligence, University of Technology Sydney (UTS), PO Box 123, 15 Broadway, Ultimo, NSW, 2007, Australia. Qinxue.Meng@uts.edu.au.
[Ti] Título:DBNorm: normalizing high-density oligonucleotide microarray data based on distributions.
[So] Source:BMC Bioinformatics;18(1):527, 2017 Nov 29.
[Is] ISSN:1471-2105
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Data from patients with rare diseases is often produced using different platforms and probe sets because patients are widely distributed in space and time. Aggregating such data requires a method of normalization that makes patient records comparable. RESULTS: This paper proposed DBNorm, implemented as an R package, is an algorithm that normalizes arbitrarily distributed data to a common, comparable form. Specifically, DBNorm merges data distributions by fitting functions to each of them, and using the probability of each element drawn from the fitted distribution to merge it into a global distribution. DBNorm contains state-of-the-art fitting functions including Polynomial, Fourier and Gaussian distributions, and also allows users to define their own fitting functions if required. CONCLUSIONS: The performance of DBNorm is compared with z-score, average difference, quantile normalization and ComBat on a set of datasets, including several that are publically available. The performance of these normalization methods are compared using statistics, visualization, and classification when class labels are known based on a number of self-generated and public microarray datasets. The experimental results show that DBNorm achieves better normalization results than conventional methods. Finally, the approach has the potential to be applicable outside bioinformatics analysis.
[Mh] Termos MeSH primário: Análise de Sequência com Séries de Oligonucleotídeos/métodos
Software
[Mh] Termos MeSH secundário: Área Sob a Curva
Regulação Neoplásica da Expressão Gênica
Seres Humanos
Distribuição Normal
Leucemia-Linfoma Linfoblástico de Células Precursoras/genética
Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia
Análise de Componente Principal
Curva ROC
Interface Usuário-Computador
[Pt] Tipo de publicação:JOURNAL ARTICLE
[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:171201
[St] Status:MEDLINE
[do] DOI:10.1186/s12859-017-1912-5


  5 / 22574 MEDLINE  
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[PMID]:27778348
[Au] Autor:Barrington-Trimis JL; Cockburn M; Metayer C; Gauderman WJ; Wiemels J; McKean-Cowdin R
[Ad] Endereço:Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA.
[Ti] Título:Trends in childhood leukemia incidence over two decades from 1992 to 2013.
[So] Source:Int J Cancer;140(5):1000-1008, 2017 Mar 01.
[Is] ISSN:1097-0215
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Incidence rates of childhood leukemia in the United States have steadily increased over the last several decades, but only recently have disparities in the increase in incidence been recognized. In the current analysis, Surveillance, Epidemiology and End Results (SEER) data were used to evaluate recent trends in the incidence of childhood leukemia diagnosed at age 0-19 years from 1992 to 2013, overall and by age, race/ethnicity, gender and histologic subtype. Hispanic White children were more likely than non-Hispanic White, non-Hispanic Black or non-Hispanic Asian children to be diagnosed with acute lymphocytic leukemia (ALL) from 2009 to 2013. From 1992 to 2013, a significant increase in ALL incidence was observed for Hispanic White children [annual percent change (APC) = 1.08, 95% CI: 0.59, 1.58]; no significant increase was observed for non-Hispanic White, Black or Asian children. ALL incidence increased by about 3% per year from 1992 to 2013 for Hispanic White children diagnosed from 15 to 19 years (APC = 2.67; 95% CI: 0.88, 4.49) and by 2% for those 10-14 years (APC = 2.09; 95% CI: 0.57, 3.63), while no significant increases in incidence were observed in non-Hispanic White, Black, or Asian children of the same age. Acute myeloid leukemia (AML) incidence increased among non-Hispanic White children under 1 year at diagnosis, and among Hispanic White children diagnosed at age 1-4. The increase in incidence rates of childhood ALL appears to be driven by rising rates in older Hispanic children (10-14, and 15-19 years). Future studies are needed to evaluate reasons for the increase in ALL among older Hispanic children.
[Mh] Termos MeSH primário: Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia
[Mh] Termos MeSH secundário: Adolescente
Distribuição por Idade
Criança
Pré-Escolar
Grupos Étnicos/estatística & dados numéricos
Feminino
Seres Humanos
Incidência
Lactente
Recém-Nascido
Masculino
Morbidade/tendências
Leucemia-Linfoma Linfoblástico de Células Precursoras/etnologia
Estudos Retrospectivos
Programa de SEER
Estados Unidos/epidemiologia
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1705
[Cu] Atualização por classe:180307
[Lr] Data última revisão:
180307
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161026
[St] Status:MEDLINE
[do] DOI:10.1002/ijc.30487


  6 / 22574 MEDLINE  
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[PMID]:29395041
[Au] Autor:Bertrand A; Favier B; Devaux Y; Goy F; Marcault-Derouard A; Veyet V; Cervos M; Schell M
[Ad] Endereço:Centre Léon-Bérard, hospitalisation à domicile pédiatrique, IHOPe, 1, place du Pr-J.-Renaut, 69373 Lyon cedex 08, France. Electronic address: amandine.bertrand@ihope.fr.
[Ti] Título:[Intravenous chemotherapy at home: A pediatric monocentric experience].
[Ti] Título:Chimiothérapie intraveineuse à domicile en cancérologie pédiatrique : une expérience monocentrique..
[So] Source:Bull Cancer;105(2):155-161, 2018 Feb.
[Is] ISSN:1769-6917
[Cp] País de publicação:France
[La] Idioma:fre
[Ab] Resumo:INTRODUCTION: Our home care unit (HCU) developed the administration of IV chemotherapy at home for some pediatric oncologic patients. METHODS: We conducted a retrospective monocentric analysis, leading to identify patients with at least one sequence of chemotherapy at home in 2015. RESULTS: Two hundred and forty four sequences of home chemotherapy have been administered in 2015. We identified two situations for home IV chemotherapy. Pediatric oncologist of day hospital prescribes the sequence. The chemotherapy is delivered at hospital for the first day. HCU takes over for the next days at home. For a sequence replacing a conventional hospitalization, the attending physician examines the patient, and confirm the clinical validation. The pediatric oncologist of HCU checks lab exams, and prescribes the chemotherapy. For both situations, IV chemotherapy is prepared by our hospital pharmacy, delivers at home or at day hospital, and HCU team manages home material and organizes hospitalization. CONCLUSIONS: This kind of organization allows setting up home IV CT for more and more patients. It allows to limit daily hospitalization for some patients living far from the hospital, and whose therapies lead to several hospitalizations.
[Mh] Termos MeSH primário: Antineoplásicos/administração & dosagem
Serviços Hospitalares de Assistência Domiciliar/organização & administração
Neoplasias/tratamento farmacológico
[Mh] Termos MeSH secundário: Antineoplásicos/uso terapêutico
Criança
Citarabina/administração & dosagem
Neoplasias Oculares/tratamento farmacológico
Feminino
Glioma/tratamento farmacológico
Acesso aos Serviços de Saúde
Neoplasias Hematológicas/tratamento farmacológico
Seres Humanos
Injeções Intravenosas/estatística & dados numéricos
Masculino
Enfermagem Oncológica
Enfermagem Pediátrica
Pediatras
Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico
Estudos Retrospectivos
Fatores de Tempo
Vimblastina/administração & dosagem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 04079A1RDZ (Cytarabine); 5V9KLZ54CY (Vinblastine)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180228
[Lr] Data última revisão:
180228
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180204
[St] Status:MEDLINE


  7 / 22574 MEDLINE  
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[PMID]:29443727
[Au] Autor:Lyu S; Zhang M; Gao Y
[Ad] Endereço:Department of Ophthalmology, West China Hospital of Sichuan University, Wuhou, Chengdu, Sichuan, China.
[Ti] Título:Acute bilateral retina hemorrhages beneath internal limiting membrane: An unusual ophthalmological case report of acute leukemia during complete clinical remission.
[So] Source:Medicine (Baltimore);97(7):e0000, 2018 Feb.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:RATIONALE: Leukemia is a common hematologic disease that causes various systemic complications, such as ophthalmological disorders. The venous congestion is considered to be the main clinical sign that occurs during the initial stage of the disease, whereas white-centered hemorrhages are the most typical manifestations in leukemic retinopathy. These complications usually manifest when the disease presents with clinical and hematological symptoms. In the present study, we report a patient who was diagnosed with leukemic retinopathy. The initial signs of this disease were bilateral hemorrhages that occurred during complete clinical remission. Previous studies regarding this condition are quite rare. PATIENT CONCERNS: We report a 26-year-old man who was diagnosed with leukemic retinopathy and exhibited the initial signs of the disease, namely bilateral hemorrhages with a distinct appearance beneath the internal limiting membrane. In addition, flame-shaped hemorrhages were observed surrounding the optic discs and/or along the vessels in the absence of venous congestion. All these changes were present during complete clinical remission. DIAGNOSES: Bilateral acute leukemic retinopathy, acute lymphoblastic leukemia (pro-B lymphocyte, BCR-ABL chimeric gene-positive). INTERVENTIONS: Clinical remission was achieved following effective systemic chemotherapy that was applied for leukemia in the hematology department. A dynamic observation was applied actively in the absence of surgery and/or medical treatment for ophthalmologic treatment. OUTCOMES: Best corrected visual acuity was 20/40 in the right eye and 20/60 in the left eye, which was considerably better than those noted at the initial visit of the patient (20/250 in the right eye and 20/400 in the left eye). LESSONS: The cautious expectant treatment is safe and helpful for acute leukemic retinopathy. A long-term follow-up is inevitable. Effective systemic chemotherapy that is required for leukemia treatment can achieve clinical remission, which might be helpful in controlling the pathological changes of the eyes.
[Mh] Termos MeSH primário: Síndromes Paraneoplásicas Oculares/complicações
Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações
Hemorragia Retiniana/etiologia
[Mh] Termos MeSH secundário: Doença Aguda
Adulto
Seres Humanos
Masculino
Retina/patologia
Hemorragia Retiniana/patologia
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180215
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000010000


  8 / 22574 MEDLINE  
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Registro de Ensaios Clínicos
Registro de Ensaios Clínicos
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[PMID]:29385376
[Au] Autor:Park JH; Rivière I; Gonen M; Wang X; Sénéchal B; Curran KJ; Sauter C; Wang Y; Santomasso B; Mead E; Roshal M; Maslak P; Davila M; Brentjens RJ; Sadelain M
[Ad] Endereço:From the Leukemia Service, Department of Medicine (J.H.P., C.S., P.M., R.J.B.), the Michael G. Harris Cell Therapy and Cell Engineering Facility (I.R., X.W., B. Sénéchal, Y.W.), the Center for Cell Engineering (J.H.P., I.R., X.W., R.J.B., M.S.), and the Departments of Epidemiology and Biostatistics
[Ti] Título:Long-Term Follow-up of CD19 CAR Therapy in Acute Lymphoblastic Leukemia.
[So] Source:N Engl J Med;378(5):449-459, 2018 02 01.
[Is] ISSN:1533-4406
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: CD19-specific chimeric antigen receptor (CAR) T cells induce high rates of initial response among patients with relapsed B-cell acute lymphoblastic leukemia (ALL) and long-term remissions in a subgroup of patients. METHODS: We conducted a phase 1 trial involving adults with relapsed B-cell ALL who received an infusion of autologous T cells expressing the 19-28z CAR at the Memorial Sloan Kettering Cancer Center (MSKCC). Safety and long-term outcomes were assessed, as were their associations with demographic, clinical, and disease characteristics. RESULTS: A total of 53 adults received 19-28z CAR T cells that were manufactured at MSKCC. After infusion, severe cytokine release syndrome occurred in 14 of 53 patients (26%; 95% confidence interval [CI], 15 to 40); 1 patient died. Complete remission was observed in 83% of the patients. At a median follow-up of 29 months (range, 1 to 65), the median event-free survival was 6.1 months (95% CI, 5.0 to 11.5), and the median overall survival was 12.9 months (95% CI, 8.7 to 23.4). Patients with a low disease burden (<5% bone marrow blasts) before treatment had markedly enhanced remission duration and survival, with a median event-free survival of 10.6 months (95% CI, 5.9 to not reached) and a median overall survival of 20.1 months (95% CI, 8.7 to not reached). Patients with a higher burden of disease (≥5% bone marrow blasts or extramedullary disease) had a greater incidence of the cytokine release syndrome and neurotoxic events and shorter long-term survival than did patients with a low disease burden. CONCLUSIONS: In the entire cohort, the median overall survival was 12.9 months. Among patients with a low disease burden, the median overall survival was 20.1 months and was accompanied by a markedly lower incidence of the cytokine release syndrome and neurotoxic events after 19-28z CAR T-cell infusion than was observed among patients with a higher disease burden. (Funded by the Commonwealth Foundation for Cancer Research and others; ClinicalTrials.gov number, NCT01044069 .).
[Mh] Termos MeSH primário: Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico
Receptores de Antígenos de Linfócitos T/uso terapêutico
Linfócitos T/imunologia
[Mh] Termos MeSH secundário: Adulto
Idoso
Citocinas/metabolismo
Seguimentos
Seres Humanos
Meia-Idade
Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade
Recidiva
Indução de Remissão
Análise de Sobrevida
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE I; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (CD19-specific chimeric antigen receptor); 0 (Cytokines); 0 (Receptors, Antigen, T-Cell)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180201
[Cl] Clinical Trial:ClinicalTrial
[St] Status:MEDLINE
[do] DOI:10.1056/NEJMoa1709919


  9 / 22574 MEDLINE  
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[PMID]:29330049
[Au] Autor:Fu Y; Yang Y; Wang X; Yin X; Zhou M; Wang S; Yang L; Huang T; Xu M; Chen C
[Ad] Endereço:Department of Hematology, Qilu Hospital, Shandong University, Jinan, Shandong, PR China. Electronic address: fuyuesdu@163.com.
[Ti] Título:The histone demethylase PHF8 promotes adult acute lymphoblastic leukemia through interaction with the MEK/ERK signaling pathway.
[So] Source:Biochem Biophys Res Commun;496(3):981-987, 2018 02 12.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Adult acute lymphoblastic leukemia (ALL) is a malignant disorder of lymphoid progenitor cells that is associated with a high risk of relapse and poor prognosis. Thus, novel pathogenic mechanisms and therapeutic targets need to be explored. Histone methylation is one of the most significant chromatin post-translational modifications. Here, we show that the histone demethylase PHF8 is highly expressed in a large number of ALL clinical specimens and that PHF8 expression is associated with ALL progression. PHF8 knockdown inhibits proliferation and promotes the apoptosis of ALL cells in vitro as well as attenuates tumor growth in vivo. PHF8 transcriptionally upregulates MEK1, a key molecule in the MEK/ERK pathway, at least partially by directly binding to its promoter, thereby activating the MEK/ERK pathway. In addition, we found that an inhibitor of the MEK/ERK pathway, PD184352, subsequently suppresses PHF8 expression. Thus, PHF8 forms a positive feedback loop with the MEK/ERK pathway, and PHF8 knockdown enhances the lethality of PD184352 in ALL cells. In conclusion, this study identifies oncogenic functions of PHF8 in adult ALL and suggests a novel epigenetic strategy for disease intervention.
[Mh] Termos MeSH primário: Carcinogênese/metabolismo
Carcinogênese/patologia
Regulação Neoplásica da Expressão Gênica
Histona Desmetilases/metabolismo
Sistema de Sinalização das MAP Quinases
Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo
Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia
Fatores de Transcrição/metabolismo
[Mh] Termos MeSH secundário: Adulto
Apoptose
Feminino
Seres Humanos
Masculino
Ligação Proteica
Células Tumorais Cultivadas
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Transcription Factors); EC 1.14.11.- (Histone Demethylases); EC 1.14.11.- (PHF8 protein, human)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180114
[St] Status:MEDLINE


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[PMID]:29254309
[Au] Autor:Tahir IM; Iqbal T; Jamil A; Saqib M
[Ad] Endereço:Pharmaceutical Research Lab, Department of Biochemistry, University of Agriculture, Faisalabad-Pakistan.
[Ti] Título:Association of BCL-2 with oxidative stress and total antioxidant status in pediatric acute lymphoblastic leukemia.
[So] Source:J Biol Regul Homeost Agents;31(4):1023-1027, 2017 Oct-Dec.
[Is] ISSN:0393-974X
[Cp] País de publicação:Italy
[La] Idioma:eng
[Ab] Resumo:B-Cell Lymphoma protein-2 (BCL-2) is one of the most studied proteins with substantial regulatory potential for both apoptosis and autophagy. BCL-2 confer chemoresistance through influencing cancer pathophysiology. Serum level of lactate dehydrogenase (LDH) predicts increased anaerobic glycolysis and is associated with metabolic modulation in cancer cells. In the present research, the interplay of BCL-2, total oxidative status (TOS) and LDH was investigated in patients with acute lymphoblastic leukemia (ALL). The studied parameters, BCL-2 protein (p less than 0.001), TOS (p less than 0.001) and LDH (p less than 0.001) were significantly elevated in the ALL group compared to the normal group (N-group). However, the total antioxidant status (TAS) was reduced significantly (p less than 0.01) in ALL patients. In the ALL group, the TOS had significant negative correlation with TAS (p less than 0.01). Furthermore, non-significant positive correlations were found between BCL-2 and LDH, BCL-2 and TAS and LDH and TAS (each with; p>0.05). However, a negative non-significant correlation was observed between BCL-2 and TOS and LDH and TOS (each with; p>0.05).
[Mh] Termos MeSH primário: Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Regulação Leucêmica da Expressão Gênica
L-Lactato Desidrogenase/genética
Leucemia-Linfoma Linfoblástico de Células Precursoras/genética
Proteínas Proto-Oncogênicas c-bcl-2/genética
[Mh] Termos MeSH secundário: Adolescente
Criança
Pré-Escolar
Feminino
Seres Humanos
Lactente
L-Lactato Desidrogenase/sangue
Masculino
Oxirredução
Estresse Oxidativo
Leucemia-Linfoma Linfoblástico de Células Precursoras/sangue
Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico
Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia
Proteínas Proto-Oncogênicas c-bcl-2/sangue
Transdução de Sinais
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (BCL2 protein, human); 0 (Proto-Oncogene Proteins c-bcl-2); EC 1.1.1.27 (L-Lactate Dehydrogenase)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171220
[St] Status:MEDLINE



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