Base de dados : MEDLINE Pesquisa : D12.776.503.921.400 [Categoria DeCS] Referências encontradas : 824 [refinar] Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 83

ir para página

1 / 824

MEDLINE

seleciona para imprimir Fotocópia Texto completo

[PMID]: 29180488 [Au] Autor: Lin A; Liang F; Thompson EA; Vono M; Ols S; Lindgren G; Hassett K; Salter H; Ciaramella G; Loré K [Ad] Endereço: Immunology and Allergy Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Solna, 171 76 Stockholm, Sweden. [Ti] Título: Rhesus Macaque Myeloid-Derived Suppressor Cells Demonstrate T Cell Inhibitory Functions and Are Transiently Increased after Vaccination. [So] Source: J Immunol;200(1):286-294, 2018 01 01. [Is] ISSN: 1550-6606 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Myeloid-derived suppressor cells (MDSCs) are major regulators of T cell responses in several pathological conditions. Whether MDSCs increase and influence T cell responses in temporary inflammation, such as after vaccine administration, is unknown. Using the rhesus macaque model, which is critical for late-stage vaccine testing, we demonstrate that monocytic (M)-MDSCs and polymorphonuclear (PMN)-MDSCs can be detected using several of the markers used in humans. However, whereas rhesus M-MDSCs lacked expression of CD33, PMN-MDSCs were identified as CD33 low-density neutrophils. Importantly, both M-MDSCs and PMN-MDSCs showed suppression of T cell proliferation in vitro. The frequency of circulating MDSCs rapidly and transiently increased 24 h after vaccine administration. M-MDSCs infiltrated the vaccine injection site, but not vaccine-draining lymph nodes. This was accompanied by upregulation of genes relevant to MDSCs such as arginase-1, IDO1, PDL1, and IL-10 at the injection site. MDSCs may therefore play a role in locally maintaining immune balance during vaccine-induced inflammation. [Mh] Termos MeSH primário: Vírus da Influenza A Subtipo H10N8/imunologia Vacinas contra Influenza/imunologia Influenza Humana/imunologia Células Supressoras Mieloides/imunologia Neutrófilos/imunologia Infecções por Orthomyxoviridae/imunologia Linfócitos T/imunologia [Mh] Termos MeSH secundário: Animais Arginase/genética Antígeno B7-H1/genética Proliferação Celular Regulação da Expressão Gênica Seres Humanos Tolerância Imunológica Indolamina-Pirrol 2,3,-Dioxigenase/genética Interleucina-10/genética Macaca mulatta Análise em Microsséries Lectina 3 Semelhante a Ig de Ligação ao Ácido Siálico/metabolismo Vacinação [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: 0 (B7-H1 Antigen); 0 (Indoleamine-Pyrrole 2,3,-Dioxygenase); 0 (Influenza Vaccines); 0 (Sialic Acid Binding Ig-like Lectin 3); 130068-27-8 (Interleukin-10); EC 3.5.3.1 (Arginase); EC 3.5.3.1 (arginase I, human) [Em] Mês de entrada: 1801 [Cu] Atualização por classe: 180131 [Lr] Data última revisão: 180131 [Sb] Subgrupo de revista: AIM; IM [Da] Data de entrada para processamento: 171129 [St] Status: MEDLINE [do] DOI: 10.4049/jimmunol.1701005

2 / 824

MEDLINE

seleciona para imprimir Fotocópia Texto completo

[PMID]: 28747436 [Au] Autor: Siddiqui SS; Springer SA; Verhagen A; Sundaramurthy V; Alisson-Silva F; Jiang W; Ghosh P; Varki A [Ad] Endereço: From the Center for Academic Research and Training in Anthropogeny (CARTA) and Glycobiology Research and Training Center (GRTC) and. [Ti] Título: The Alzheimer's disease-protective CD33 splice variant mediates adaptive loss of function via diversion to an intracellular pool. [So] Source: J Biol Chem;292(37):15312-15320, 2017 09 15. [Is] ISSN: 1083-351X [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: The immunomodulatory receptor Siglec-3/CD33 influences risk for late-onset Alzheimer's disease (LOAD), an apparently human-specific post-reproductive disease. generates two splice variants: a full-length CD33M transcript produced primarily by the "LOAD-risk" allele and a shorter CD33m isoform lacking the sialic acid-binding domain produced primarily from the "LOAD-protective" allele. An SNP that modulates CD33 splicing to favor CD33m is associated with enhanced microglial activity. Individuals expressing more protective isoform accumulate less brain ß-amyloid and have a lower LOAD risk. How the CD33m isoform increases ß-amyloid clearance remains unknown. We report that the protection by the CD33m isoform may not be conferred by what it does but, rather, from what it cannot do. Analysis of blood neutrophils and monocytes and a microglial cell line revealed that unlike CD33M, the CD33m isoform does not localize to cell surfaces; instead, it accumulates in peroxisomes. Cell stimulation and activation did not mobilize CD33m to the surface. Thus, the CD33m isoform may neither interact directly with amyloid plaques nor engage in cell-surface signaling. Rather, production and localization of CD33m in peroxisomes is a way of diminishing the amount of CD33M and enhancing ß-amyloid clearance. We confirmed intracellular localization by generating a CD33m-specific monoclonal antibody. Of note, CD33 is the only Siglec with a peroxisome-targeting sequence, and this motif emerged by convergent evolution in toothed whales, the only other mammals with a prolonged post-reproductive lifespan. The allele that protects post-reproductive individuals from LOAD may have evolved by adaptive loss-of-function, an example of the less-is-more hypothesis. [Mh] Termos MeSH primário: Doença de Alzheimer/genética Predisposição Genética para Doença Macrófagos/metabolismo Microglia/metabolismo Neutrófilos/metabolismo Polimorfismo de Nucleotídeo Único Lectina 3 Semelhante a Ig de Ligação ao Ácido Siálico/metabolismo [Mh] Termos MeSH secundário: Alelos Doença de Alzheimer/imunologia Doença de Alzheimer/metabolismo Doença de Alzheimer/patologia Motivos de Aminoácidos Proteínas de Bactérias/metabolismo Proteínas de Bactérias/toxicidade Linhagem Celular Membrana Celular/efeitos dos fármacos Membrana Celular/metabolismo Membrana Celular/patologia Seres Humanos Lipopolissacarídeos/toxicidade Ativação de Macrófagos/efeitos dos fármacos Macrófagos/efeitos dos fármacos Macrófagos/imunologia Macrófagos/patologia Microglia/citologia Microglia/imunologia Microglia/patologia N-Formilmetionina Leucil-Fenilalanina/toxicidade Proteínas do Tecido Nervoso/química Proteínas do Tecido Nervoso/genética Proteínas do Tecido Nervoso/metabolismo Neuraminidase/metabolismo Neuraminidase/toxicidade Ativação de Neutrófilo/efeitos dos fármacos Neutrófilos/efeitos dos fármacos Neutrófilos/imunologia Neutrófilos/patologia Peroxissomos/efeitos dos fármacos Peroxissomos/metabolismo Peroxissomos/patologia Filogenia Domínios e Motivos de Interação entre Proteínas Isoformas de Proteínas/química Isoformas de Proteínas/genética Isoformas de Proteínas/metabolismo Sinais Direcionadores de Proteínas Transporte Proteico/efeitos dos fármacos Lectina 3 Semelhante a Ig de Ligação ao Ácido Siálico/química Lectina 3 Semelhante a Ig de Ligação ao Ácido Siálico/genética [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL [Nm] Nome de substância: 0 (Bacterial Proteins); 0 (CD33 protein, human); 0 (Lipopolysaccharides); 0 (Nerve Tissue Proteins); 0 (Protein Isoforms); 0 (Protein Sorting Signals); 0 (Sialic Acid Binding Ig-like Lectin 3); 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine); EC 3.2.1.18 (Neuraminidase) [Em] Mês de entrada: 1709 [Cu] Atualização por classe: 171230 [Lr] Data última revisão: 171230 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170728 [St] Status: MEDLINE [do] DOI: 10.1074/jbc.M117.799346

3 / 824

MEDLINE

seleciona para imprimir Fotocópia Texto completo

[PMID]: 28668350 [Au] Autor: Laing AA; Harrison CJ; Gibson BES; Keeshan K [Ad] Endereço: Paul O'Gorman Leukaemia Research Centre, Institute of Cancer Sciences, University of Glasgow, Scotland, UK. [Ti] Título: Unlocking the potential of anti-CD33 therapy in adult and childhood acute myeloid leukemia. [So] Source: Exp Hematol;54:40-50, 2017 Oct. [Is] ISSN: 1873-2399 [Cp] País de publicação: Netherlands [La] Idioma: eng [Ab] Resumo: Acute myeloid leukemia (AML) develops when there is a block in differentiation and uncontrolled proliferation of myeloid precursors, resulting in bone marrow failure. AML is a clinically, morphologically, and genetically heterogeneous disease, and biological differences between adult and childhood AML have been identified. AML comprises 15%-20% of all children <15 years of age diagnosed with acute leukemia. Relapse occurs in up to 40% of children with AML and is the most common cause of death. Relapse arises from leukemic stem cells (LSCs) that persist after conventional chemotherapy. The treatment of AML is challenging, and new strategies to target LSCs are required. The cell surface marker CD33 has been identified as a therapeutic target, and novel anti-CD33 immunotherapies are promising new agents in the treatment of AML. This review summarizes recent developments emphasizing the genetic differences in adult and childhood AML and highlights the rationale for CD33 as a target for therapy in all age groups. [Mh] Termos MeSH primário: Anticorpos Monoclonais/uso terapêutico Antineoplásicos/uso terapêutico Biomarcadores Tumorais/genética Leucemia Mieloide Aguda/tratamento farmacológico Terapia de Alvo Molecular Células-Tronco Neoplásicas/efeitos dos fármacos Lectina 3 Semelhante a Ig de Ligação ao Ácido Siálico/genética [Mh] Termos MeSH secundário: Adulto Fatores Etários Biomarcadores Tumorais/antagonistas & inibidores Biomarcadores Tumorais/metabolismo Proliferação Celular/efeitos dos fármacos Criança Resistência a Medicamentos Antineoplásicos/genética Expressão Gênica Seres Humanos Imunoterapia/métodos Leucemia Mieloide Aguda/genética Leucemia Mieloide Aguda/imunologia Leucemia Mieloide Aguda/patologia Células Mieloides/efeitos dos fármacos Células Mieloides/metabolismo Células Mieloides/patologia Células-Tronco Neoplásicas/metabolismo Células-Tronco Neoplásicas/patologia Lectina 3 Semelhante a Ig de Ligação ao Ácido Siálico/antagonistas & inibidores Lectina 3 Semelhante a Ig de Ligação ao Ácido Siálico/metabolismo [Pt] Tipo de publicação: JOURNAL ARTICLE; REVIEW [Nm] Nome de substância: 0 (Antibodies, Monoclonal); 0 (Antineoplastic Agents); 0 (Biomarkers, Tumor); 0 (CD33 protein, human); 0 (Sialic Acid Binding Ig-like Lectin 3) [Em] Mês de entrada: 1710 [Cu] Atualização por classe: 171004 [Lr] Data última revisão: 171004 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170703 [St] Status: MEDLINE

4 / 824

MEDLINE

seleciona para imprimir Fotocópia Texto completo

[PMID]: 28644774 [Au] Autor: Lamba JK; Chauhan L; Shin M; Loken MR; Pollard JA; Wang YC; Ries RE; Aplenc R; Hirsch BA; Raimondi SC; Walter RB; Bernstein ID; Gamis AS; Alonzo TA; Meshinchi S [Ad] Endereço: Jatinder K. Lamba, Lata Chauhan, and Miyoung Shin, University of Florida, Gainesville, FL; Michael R. Loken, Hematologics Inc; Rhonda E. Ries, Irwin D. Bernstein, and Soheil Meshinchi, Fred Hutchinson Cancer Research Center; Roland B. Walter and Soheil Meshinchi, University of Washington, Seattle, W [Ti] Título: CD33 Splicing Polymorphism Determines Gemtuzumab Ozogamicin Response in De Novo Acute Myeloid Leukemia: Report From Randomized Phase III Children's Oncology Group Trial AAML0531. [So] Source: J Clin Oncol;35(23):2674-2682, 2017 Aug 10. [Is] ISSN: 1527-7755 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Purpose Gemtuzumab ozogamicin (GO), a CD33-targeted immunoconjugate, is a re-emerging therapy for acute myeloid leukemia (AML). CD33 single nucleotide polymorphism rs12459419 C>T in the splice enhancer region regulates the expression of an alternatively spliced CD33 isoform lacking exon2 (D2-CD33), thus eliminating the CD33 IgV domain, which is the antibody-binding site for GO, as well as diagnostic immunophenotypic panels. We aimed to determine the impact of the genotype of this splicing polymorphism in patients with AML treated with GO-containing chemotherapy. Patients and Methods CD33 splicing single nucleotide polymorphism was evaluated in newly diagnosed patients with AML randomly assigned to receive standard five-course chemotherapy alone (No-GO arm, n = 408) or chemotherapy with the addition of two doses of GO once during induction and once during intensification (GO arm, n = 408) as per the Children's Oncology Group AAML0531 trial. Results The rs12459419 genotype was CC in 415 patients (51%), CT in 316 patients (39%), and TT in 85 patients (10%), with a minor allele frequency of 30%. The T allele was significantly associated with higher levels of D2-CD33 transcript ( P < 1.0E ) and with lower diagnostic leukemic cell surface CD33 intensity ( P < 1.0E ). Patients with the CC genotype had significantly lower relapse risk in the GO arm than in the No-GO arm (26% v 49%; P < .001). However, in patients with the CT or TT genotype, exposure to GO did not influence relapse risk (39% v 40%; P = .85). Disease-free survival was higher in patients with the CC genotype in the GO arm than in the No-GO arm (65% v 46%, respectively; P = .004), but this benefit of GO addition was not seen in patients with the CT or TT genotype. Conclusion Our results suggest that patients with the CC genotype for rs12459419 have a substantial response to GO, making this a potential biomarker for the selection of patients with a likelihood of significant response to GO. [Mh] Termos MeSH primário: Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico Leucemia Mieloide Aguda/tratamento farmacológico Leucemia Mieloide Aguda/genética RNA Mensageiro/sangue Lectina 3 Semelhante a Ig de Ligação ao Ácido Siálico/genética [Mh] Termos MeSH secundário: Adolescente Adulto Alelos Aminoglicosídeos/administração & dosagem Anticorpos Monoclonais Humanizados/administração & dosagem Criança Pré-Escolar Intervalo Livre de Doença Heterozigoto Homozigoto Seres Humanos Lactente Recém-Nascido Leucemia Mieloide Aguda/metabolismo Polimorfismo de Nucleotídeo Único Lectina 3 Semelhante a Ig de Ligação ao Ácido Siálico/metabolismo Resultado do Tratamento Adulto Jovem [Pt] Tipo de publicação: CLINICAL TRIAL, PHASE III; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL [Nm] Nome de substância: 0 (Aminoglycosides); 0 (Antibodies, Monoclonal, Humanized); 0 (RNA, Messenger); 0 (Sialic Acid Binding Ig-like Lectin 3); 93NS566KF7 (gemtuzumab) [Em] Mês de entrada: 1709 [Cu] Atualização por classe: 170908 [Lr] Data última revisão: 170908 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170624 [St] Status: MEDLINE [do] DOI: 10.1200/JCO.2016.71.2513

5 / 824

MEDLINE

seleciona para imprimir Fotocópia Texto completo

[PMID]: 28607471 [Au] Autor: Godwin CD; Gale RP; Walter RB [Ad] Endereço: Hematology/Oncology Fellowship Program, University of Washington, Seattle, WA, USA. [Ti] Título: Gemtuzumab ozogamicin in acute myeloid leukemia. [So] Source: Leukemia;31(9):1855-1868, 2017 Sep. [Is] ISSN: 1476-5551 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: CD33 is variably expressed on leukemia blasts in almost all patients with acute myeloid leukemia (AML) and possibly leukemia stem cells in some. Efforts to target CD33 therapeutically have focused on gemtuzumab ozogamicin (GO; Mylotarg), an antibody-drug conjugate delivering a DNA-damaging calicheamicin derivative. GO is most effective in acute promyelocytic leukemia but induces remissions in other AML types and received accelerated approval in the US in 2000. However, because a large follow-up study showed no survival improvement and increased early deaths the drug manufacturer voluntarily withdrew the US New Drug Application in 2010. More recently, a meta-analysis of data from several trials reported better survival in adults with favorable- and intermediate-risk cytogenetics but not adverse-risk AML randomized to receive GO along with intensive induction chemotherapy. As a result, GO is being re-evaluated by regulatory agencies. Responses to GO are diverse and predictive biological response markers are needed. Besides cytogenetic risk, ATP-binding cassette transporter activity and possibly CD33 display on AML blasts may predict response, but established clinical assays and prospective validation are lacking. Single-nucleotide polymorphisms in CD33 may also be predictive, most notably rs12459419 where the minor T-allele leads to decreased display of full-length CD33 and preferential translation of a splice variant not recognized by GO. Data from retrospective analyses suggest only patients with the rs12459419 CC genotype may benefit from GO therapy but confirmation is needed. Most important may be markers for AML cell sensitivity to calicheamicin, which varies over 100 000-fold, but useful assays are unavailable. Novel CD33-targeted drugs may overcome some of GO's limitations but it is currently unknown whether such drugs will be more effective in patients benefitting from GO and/or improve outcomes in patients not benefitting from GO, and what the supportive care requirements will be to enable their safe use. [Mh] Termos MeSH primário: Aminoglicosídeos/uso terapêutico Anticorpos Monoclonais Humanizados/uso terapêutico Leucemia Mieloide Aguda/tratamento farmacológico [Mh] Termos MeSH secundário: Genótipo Seres Humanos Leucemia Mieloide Aguda/genética Leucemia Mieloide Aguda/mortalidade Polimorfismo de Nucleotídeo Único Prognóstico Lectina 3 Semelhante a Ig de Ligação ao Ácido Siálico/efeitos dos fármacos [Pt] Tipo de publicação: JOURNAL ARTICLE; REVIEW [Nm] Nome de substância: 0 (Aminoglycosides); 0 (Antibodies, Monoclonal, Humanized); 0 (CD33 protein, human); 0 (Sialic Acid Binding Ig-like Lectin 3); 93NS566KF7 (gemtuzumab) [Em] Mês de entrada: 1709 [Cu] Atualização por classe: 170928 [Lr] Data última revisão: 170928 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170614 [St] Status: MEDLINE [do] DOI: 10.1038/leu.2017.187

6 / 824

MEDLINE

seleciona para imprimir Fotocópia Texto completo

[PMID]: 28504999 [Au] Autor: Mitteldorf C; Berisha A; Pfaltz MC; Broekaert SMC; Schön MP; Kerl K; Kempf W [Ad] Endereço: *Department of Dermatology, HELIOS-Klinikum Hildesheim, Hildesheim †Kempf und Pfaltz, Histologische Diagnostik §Department of Dermatology, Venereology and Allergology, Lower Saxony Institute of Occupational Dermatology, University Medical Center Göttingen, Göttingen, Germany Departments of ‡Psychiatry and Psychotherapy ¶Dermatology, University Hospital Zürich, Zürich, Switzerland. [Ti] Título: Tumor Microenvironment and Checkpoint Molecules in Primary Cutaneous Diffuse Large B-Cell Lymphoma-New Therapeutic Targets. [So] Source: Am J Surg Pathol;41(7):998-1004, 2017 Jul. [Is] ISSN: 1532-0979 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Programmed death ligand 1 (PD-L1) is expressed by 20% to 57% of systemic diffuse large B cell lymphomas (DLBCLs). PD-L1 expression in primary cutaneous DLBCL (pcDLBCL) has not been studied so far. Sixteen paraffin-embedded tissue samples of pcDLBCL (13 leg type [LT], 3 others [OT]) were investigated for PD-1, PD-L1, and CD33 expression and the cellular composition of the tumor microenvironment, focusing on myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages. Membrane-bound PD-L1 expression by the tumor cells was observed in all samples, albeit to a variable extent (19.9%). As expected, most DLBCL-LT (10 cases) were classified as activated B cell like type, with a higher PD-L1 score (21.9%) compared with that of the germinal center B cell like type (7.7%). The surrounding infiltrate consisted predominately of CD163(+) M2 rather than CD68(+) macrophages (CD68:CD163=1:4 to 6). Moreover, a considerable proportion of CD33(+) MDSCs with PD-L1 coexpression was admixed. Tumor cells expressed CD33 to variable degrees (2% to 60%). The number of MDSCs or M2 macrophages did not correlate with pcDLBCL subtypes LT or OT. T cells were only a minor component of the tumor microenvironment. We propose that PD-L1(+) tumor cells and PD-L1(+) MDSCs shield the tumor against PD-1(+) tumor-infiltrating lymphocytes, consequently leading to inhibition and diminution of tumor-infiltrating lymphocytes. Moreover, we found a polarization to M2 macrophages, which may contribute to the poor prognosis of DLBCL patients. Thus, targeting of tumor cells and MDSCs using anti-PD-1/anti-PD-L1 or anti-CD33 antibodies might be a worthwhile new approach to treat this aggressive form of cutaneous B-cell lymphoma. [Mh] Termos MeSH primário: Antígeno B7-H1/metabolismo Biomarcadores Tumorais/metabolismo Linfoma Difuso de Grandes Células B/patologia Receptor de Morte Celular Programada 1/metabolismo Lectina 3 Semelhante a Ig de Ligação ao Ácido Siálico/metabolismo Neoplasias Cutâneas/patologia Microambiente Tumoral [Mh] Termos MeSH secundário: Adulto Idoso Idoso de 80 Anos ou mais Estudos de Casos e Controles Feminino Seres Humanos Linfoma Difuso de Grandes Células B/metabolismo Masculino Meia-Idade Estudos Retrospectivos Neoplasias Cutâneas/metabolismo [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (B7-H1 Antigen); 0 (Biomarkers, Tumor); 0 (CD274 protein, human); 0 (CD33 protein, human); 0 (PDCD1 protein, human); 0 (Programmed Cell Death 1 Receptor); 0 (Sialic Acid Binding Ig-like Lectin 3) [Em] Mês de entrada: 1709 [Cu] Atualização por classe: 171116 [Lr] Data última revisão: 171116 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170516 [St] Status: MEDLINE [do] DOI: 10.1097/PAS.0000000000000851

7 / 824

MEDLINE

seleciona para imprimir Fotocópia

[PMID]: 28391288 [Au] Autor: Jiang Y; Xu P; Yao D; Chen X; Dai H [Ad] Endereço: Department of Hematology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China (mainland). [Ti] Título: CD33, CD96 and Death Associated Protein Kinase (DAPK) Expression Are Associated with the Survival Rate and/or Response to the Chemotherapy in the Patients with Acute Myeloid Leukemia (AML). [So] Source: Med Sci Monit;23:1725-1732, 2017 Apr 09. [Is] ISSN: 1643-3750 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: BACKGROUND Leukemia stem cells (LSC) are involved in the incidence, drug resistance, and relapse of leukemia while LSC-related antigen CD33, CD96, and DAPK expression in AML and its prognosis is still unclear. This study explored LSC-related antigens expression in acute myeloid leukemia (AML) and its prognosis. MATERIAL AND METHODS A total of 156 cases of AML patients were enrolled in the experiment. The expression of CD33, CD96, and DAPK in CD34+CD38-CD123+ LSC were tested by flow cytometry. The survival curve was established using the Kaplan-Meier method. RESULTS Among different subtypes of AML, the positive rate of CD33 was M3> M5> M1> M2> M4; for CD96 it was M5> M4> M2> M3> M1; and for DAPK it was M3> M2> M5> M4> M1. After chemotherapy, the response rate in CD33 and CD96 high expression groups, and DAPK low expression group was significantly lower than the groups with CD33 low expression, CD96 low expression, and DAPK high expression. The median survival time in the CD33 high expression group was markedly lower than the CD33 low expression group (36.5 months). The CD96 high expression group exhibited obviously shorter median survival time than the CD96 low expression group. The DAPK high expression group exhibited longer median survival time than the DAPK low expression group. CONCLUSIONS CD33 and CD96 overexpression, and DAPK downregulation in the LSC of AML patients were associated with poor chemotherapy effect and prognosis, and higher recurrence rate. [Mh] Termos MeSH primário: Células da Medula Óssea/metabolismo Leucemia Mieloide Aguda/tratamento farmacológico Leucemia Mieloide Aguda/metabolismo [Mh] Termos MeSH secundário: Adolescente Adulto Antígenos CD/genética Antígenos CD/metabolismo Biomarcadores Farmacológicos Células da Medula Óssea/imunologia Proteínas Quinases Associadas com Morte Celular/genética Proteínas Quinases Associadas com Morte Celular/metabolismo Feminino Citometria de Fluxo Regulação Neoplásica da Expressão Gênica Predisposição Genética para Doença Seres Humanos Leucemia Mieloide Aguda/genética Leucemia Mieloide Aguda/imunologia Masculino Meia-Idade Células-Tronco Neoplásicas/imunologia Células-Tronco Neoplásicas/metabolismo Prognóstico Lectina 3 Semelhante a Ig de Ligação ao Ácido Siálico/genética Lectina 3 Semelhante a Ig de Ligação ao Ácido Siálico/metabolismo Taxa de Sobrevida [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Antigens, CD); 0 (Biomarkers, Pharmacological); 0 (CD33 protein, human); 0 (CD97 protein, human); 0 (Sialic Acid Binding Ig-like Lectin 3); EC 2.7.11.1 (Death-Associated Protein Kinases) [Em] Mês de entrada: 1706 [Cu] Atualização por classe: 170630 [Lr] Data última revisão: 170630 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170410 [St] Status: MEDLINE

8 / 824

MEDLINE

seleciona para imprimir Fotocópia Texto completo

[PMID]: 28361465 [Au] Autor: Lambert JM; Morris CQ [Ad] Endereço: ImmunoGen, Inc., Waltham, MA, USA. John.Lambert@immunogen.com. [Ti] Título: Antibody-Drug Conjugates (ADCs) for Personalized Treatment of Solid Tumors: A Review. [So] Source: Adv Ther;34(5):1015-1035, 2017 May. [Is] ISSN: 1865-8652 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Attaching a cytotoxic "payload" to an antibody to form an antibody-drug conjugate (ADC) provides a mechanism for selective delivery of the cytotoxic agent to cancer cells via the specific binding of the antibody to cancer-selective cell surface molecules. The first ADC to receive marketing authorization was gemtuzumab ozogamicin, which comprises an anti-CD33 antibody conjugated to a highly potent DNA-targeting antibiotic, calicheamicin, approved in 2000 for treating acute myeloid leukemia. It was withdrawn from the US market in 2010 following an unsuccessful confirmatory trial. The development of two classes of highly potent microtubule-disrupting agents, maytansinoids and auristatins, as payloads for ADCs resulted in approval of brentuximab vedotin in 2011 for treating Hodgkin lymphoma and anaplastic large cell lymphoma, and approval of ado-trastuzumab emtansine in 2013 for treating HER2-positive breast cancer. Their success stimulated much research into the ADC approach, with >60 ADCs currently in clinical evaluation, mostly targeting solid tumors. Five ADCs have advanced into pivotal clinical trials for treating various solid tumors-platinum-resistant ovarian cancer, mesothelioma, triple-negative breast cancer, glioblastoma, and small cell lung cancer. The level of target expression is a key parameter in predicting the likelihood of patient benefit for all these ADCs, as well as for the approved compound, ado-trastuzumab emtansine. The development of a patient selection strategy linked to target expression on the tumor is thus critically important for identifying the population appropriate for receiving treatment. [Mh] Termos MeSH primário: Aminobenzoatos/uso terapêutico Aminoglicosídeos/uso terapêutico Anticorpos Monoclonais Humanizados/uso terapêutico Antineoplásicos/uso terapêutico Imunoconjugados/uso terapêutico Maitansina/análogos & derivados Neoplasias/tratamento farmacológico Oligopeptídeos/uso terapêutico Lectina 3 Semelhante a Ig de Ligação ao Ácido Siálico/uso terapêutico [Mh] Termos MeSH secundário: Seres Humanos Maitansina/uso terapêutico Neoplasias/imunologia Trastuzumab [Pt] Tipo de publicação: JOURNAL ARTICLE; REVIEW [Nm] Nome de substância: 0 (Aminobenzoates); 0 (Aminoglycosides); 0 (Antibodies, Monoclonal, Humanized); 0 (Antineoplastic Agents); 0 (Immunoconjugates); 0 (Oligopeptides); 0 (Sialic Acid Binding Ig-like Lectin 3); 0 (auristatin); 14083FR882 (Maytansine); 93NS566KF7 (gemtuzumab); P188ANX8CK (Trastuzumab); SE2KH7T06F (ado-trastuzumab emtansine) [Em] Mês de entrada: 1710 [Cu] Atualização por classe: 171116 [Lr] Data última revisão: 171116 [Sb] Subgrupo de revista: T [Da] Data de entrada para processamento: 170401 [St] Status: MEDLINE [do] DOI: 10.1007/s12325-017-0519-6

9 / 824

MEDLINE

seleciona para imprimir Fotocópia Texto completo

[PMID]: 28205451 [Au] Autor: Zaric SS; Lappin MJ; Fulton CR; Lundy FT; Coulter WA; Irwin CR [Ad] Endereço: 1 Plymouth University, Peninsula Schools of Medicine and Dentistry, Plymouth, UK. [Ti] Título: Sialylation of Porphyromonas gingivalis LPS and its effect on bacterial-host interactions. [So] Source: Innate Immun;23(3):319-326, 2017 Apr. [Is] ISSN: 1753-4267 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Porphyromonas gingivalis produces different LPS isoforms with significant structural variations of their lipid A and O-antigen moieties that can affect its pro-inflammatory and bone-resorbing potential. We show here, for the first time, that P. gingivalis LPS isolated from W83 strain is highly sialylated and possesses significantly reduced inflammatory potential compared with less sialylated ATCC 33277 strain LPS. Nevertheless, the reduction in the endotoxin activity is not mediated by the presence of sialic acid LPS moieties as the sialic acid-free LPS produced by the mutant W83 strain exhibits a similar inflammatory potential to the wild type strain. Furthermore, our findings suggest that the interaction between the sialic acid LPS moieties and the inhibitory CD33 receptor is prevented by endogenously expressed sialic acid on the surface of THP-1 cells that cannot be out-competed by sialic acid containing P. gingivalis LPS. The present study also highlights the importance of endogenous sialic acid as a 'self-associated molecular pattern' and CD33 receptors in modulation of innate immune response as human gingival fibroblasts, which do not express CD33 receptors, and desialylated THP-1 cells have both been found to have much higher spontaneous IL-8 production than naïve THP-1 cells. [Mh] Termos MeSH primário: Infecções por Bacteroidaceae/imunologia Fibroblastos/imunologia Gengiva/patologia Lipopolissacarídeos/imunologia Monócitos/imunologia Ácido N-Acetilneuramínico/metabolismo Doenças Periodontais/imunologia Porphyromonas gingivalis/metabolismo [Mh] Termos MeSH secundário: Linhagem Celular Fibroblastos/microbiologia Interações Hospedeiro-Patógeno Seres Humanos Imunidade Inata Interleucina-8/metabolismo Lipídeo A/química Lipopolissacarídeos/química Monócitos/microbiologia Mutação/genética Ácido N-Acetilneuramínico/química Antígenos O/química Porphyromonas gingivalis/genética Porphyromonas gingivalis/imunologia Processamento de Proteína Pós-Traducional Lectina 3 Semelhante a Ig de Ligação ao Ácido Siálico/metabolismo [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Interleukin-8); 0 (Lipid A); 0 (Lipopolysaccharides); 0 (O Antigens); 0 (Sialic Acid Binding Ig-like Lectin 3); GZP2782OP0 (N-Acetylneuraminic Acid) [Em] Mês de entrada: 1706 [Cu] Atualização por classe: 170626 [Lr] Data última revisão: 170626 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170217 [St] Status: MEDLINE [do] DOI: 10.1177/1753425917694245

10 / 824

MEDLINE

seleciona para imprimir Fotocópia Texto completo

[PMID]: 28157217 [Au] Autor: Hoseini SS; Cheung NK [Ad] Endereço: Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA. [Ti] Título: Acute myeloid leukemia targets for bispecific antibodies. [So] Source: Blood Cancer J;7(2):e522, 2017 Feb 03. [Is] ISSN: 2044-5385 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Despite substantial gains in our understanding of the genomics of acute myelogenous leukemia (AML), patient survival remains unsatisfactory especially among the older age group. T cell-based therapy of lymphoblastic leukemia is rapidly advancing; however, its application in AML is still lagging behind. Bispecific antibodies can redirect polyclonal effector cells to engage chosen targets on leukemia blasts. When the effector cells are natural-killer cells, both antibody-dependent and antibody-independent mechanisms could be exploited. When the effectors are T cells, direct tumor cytotoxicity can be engaged followed by a potential vaccination effect. In this review, we summarize the AML-associated tumor targets and the bispecific antibodies that have been studied. The potentials and limitations of each of these systems will be discussed. [Mh] Termos MeSH primário: Anticorpos Biespecíficos/uso terapêutico Leucemia Mieloide Aguda/tratamento farmacológico Lectina 3 Semelhante a Ig de Ligação ao Ácido Siálico/genética [Mh] Termos MeSH secundário: Seres Humanos Leucemia Mieloide Aguda/patologia Meia-Idade Células Tumorais Cultivadas [Pt] Tipo de publicação: JOURNAL ARTICLE; REVIEW [Nm] Nome de substância: 0 (Antibodies, Bispecific); 0 (Sialic Acid Binding Ig-like Lectin 3) [Em] Mês de entrada: 1711 [Cu] Atualização por classe: 171106 [Lr] Data última revisão: 171106 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170204 [St] Status: MEDLINE [do] DOI: 10.1038/bcj.2017.2

---

página 1 de 83

ir para página

Refinar a pesquisa

Base de dados : MEDLINE

Formulário avançado

		Pesquisar	no campo
1			PalavrasDescritor de assuntoDescritor de assunto primárioLimitesAutorPalavras do títuloPalavras do resumoIdiomaPaís de publicaçãoNome de substânciaNome de pessoa como assuntoRevistaAssunto de RevistaISSNTipo de publicaçãoIdentificador únicoMês de entradaAno de publicaçãoTexto completoAtualização por classeCategoria DeCSCategoria DeCS explodidaCategoria CID-10SubSetsPais de AfiliaçãoAfiliaçãoAfiliação 2
2	and or and not		PalavrasDescritor de assuntoDescritor de assunto primárioLimitesAutorPalavras do títuloPalavras do resumoIdiomaPaís de publicaçãoNome de substânciaNome de pessoa como assuntoRevistaAssunto de RevistaISSNTipo de publicaçãoIdentificador únicoMês de entradaAno de publicaçãoTexto completoAtualização por classeCategoria DeCSCategoria DeCS explodidaCategoria CID-10SubSetsPais de AfiliaçãoAfiliaçãoAfiliação 2
3	and or and not		PalavrasDescritor de assuntoDescritor de assunto primárioLimitesAutorPalavras do títuloPalavras do resumoIdiomaPaís de publicaçãoNome de substânciaNome de pessoa como assuntoRevistaAssunto de RevistaISSNTipo de publicaçãoIdentificador únicoMês de entradaAno de publicaçãoTexto completoAtualização por classeCategoria DeCSCategoria DeCS explodidaCategoria CID-10SubSetsPais de AfiliaçãoAfiliaçãoAfiliação 2

Search engine: iAH v2.6 powered by WWWISIS

BIREME/OPAS/OMS - Centro Latino-Americano e do Caribe de Informação em Ciências da Saúde