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[PMID]:28678791
[Au] Autor:Charych D; Khalili S; Dixit V; Kirk P; Chang T; Langowski J; Rubas W; Doberstein SK; Eldon M; Hoch U; Zalevsky J
[Ad] Endereço:Nektar Therapeutics, San Francisco, California, United States of America.
[Ti] Título:Modeling the receptor pharmacology, pharmacokinetics, and pharmacodynamics of NKTR-214, a kinetically-controlled interleukin-2 (IL2) receptor agonist for cancer immunotherapy.
[So] Source:PLoS One;12(7):e0179431, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Cytokines are potent immune modulating agents but are not ideal medicines in their natural form due to their short half-life and pleiotropic systemic effects. NKTR-214 is a clinical-stage biologic that comprises interleukin-2 (IL2) protein bound by multiple releasable polyethylene glycol (PEG) chains. In this highly PEG-bound form, the IL2 is inactive; therefore, NKTR-214 is a biologic prodrug. When administered in vivo, the PEG chains slowly release, creating a cascade of increasingly active IL2 protein conjugates bound by fewer PEG chains. The 1-PEG-IL2 and 2-PEG-IL2 species derived from NKTR-214 are the most active conjugated-IL2 species. Free-IL2 protein is undetectable in vivo as it is eliminated faster than formed. The PEG chains on NKTR-214 are located at the region of IL2 that contacts the alpha (α) subunit of the heterotrimeric IL2 receptor complex, IL2Rαßγ, reducing its ability to bind and activate the heterotrimer. The IL2Rαßγ complex is constitutively expressed on regulatory T cells (Tregs). Therefore, without the use of mutations, PEGylation reduces the affinity for IL2Rαßγ to a greater extent than for IL2Rßγ, the receptor complex predominant on CD8 T cells. NKTR-214 treatment in vivo favors activation of CD8 T cells over Tregs in the tumor microenvironment to provide anti-tumor efficacy in multiple syngeneic models. Mechanistic modeling based on in vitro and in vivo kinetic data provides insight into the mechanism of NKTR-214 pharmacology. The model reveals that conjugated-IL2 protein derived from NKTR-214 occupy IL-2Rßγ to a greater extent compared to free-IL2 protein. The model accurately describes the sustained in vivo signaling observed after a single dose of NKTR-214 and explains how the properties of NKTR-214 impart a unique kinetically-controlled immunological mechanism of action.
[Mh] Termos MeSH primário: Imunoterapia/métodos
Interleucina-2/análogos & derivados
Neoplasias/terapia
Polietilenoglicóis/farmacologia
Receptores de Interleucina-2/agonistas
[Mh] Termos MeSH secundário: Algoritmos
Animais
Linfócitos T CD8-Positivos/efeitos dos fármacos
Linfócitos T CD8-Positivos/imunologia
Linfócitos T CD8-Positivos/metabolismo
Linhagem Celular Tumoral
Liberação Controlada de Fármacos
Feminino
Subunidade gama Comum de Receptores de Interleucina/agonistas
Subunidade gama Comum de Receptores de Interleucina/metabolismo
Interleucina-2/farmacocinética
Interleucina-2/farmacologia
Subunidade alfa de Receptor de Interleucina-2/agonistas
Subunidade alfa de Receptor de Interleucina-2/metabolismo
Subunidade beta de Receptor de Interleucina-2/agonistas
Subunidade beta de Receptor de Interleucina-2/metabolismo
Cinética
Camundongos Endogâmicos BALB C
Camundongos Endogâmicos C3H
Camundongos Endogâmicos C57BL
Modelos Teóricos
Neoplasias/imunologia
Neoplasias/metabolismo
Fosforilação/efeitos dos fármacos
Polietilenoglicóis/farmacocinética
Pró-Fármacos/farmacocinética
Pró-Fármacos/farmacologia
Receptores de Interleucina-2/metabolismo
Fator de Transcrição STAT5/metabolismo
Linfócitos T Reguladores/efeitos dos fármacos
Linfócitos T Reguladores/imunologia
Linfócitos T Reguladores/metabolismo
Transplante Homólogo
Microambiente Tumoral/efeitos dos fármacos
Microambiente Tumoral/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Il2rg protein, mouse); 0 (Interleukin Receptor Common gamma Subunit); 0 (Interleukin-2); 0 (Interleukin-2 Receptor alpha Subunit); 0 (Interleukin-2 Receptor beta Subunit); 0 (NKTR-214); 0 (Prodrugs); 0 (Receptors, Interleukin-2); 0 (STAT5 Transcription Factor); 30IQX730WE (Polyethylene Glycols)
[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:170706
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0179431


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[PMID]:28646117
[Au] Autor:Narita T; Ishida T; Ito A; Masaki A; Kinoshita S; Suzuki S; Takino H; Yoshida T; Ri M; Kusumoto S; Komatsu H; Imada K; Tanaka Y; Takaori-Kondo A; Inagaki H; Scholz A; Lienau P; Kuroda T; Ueda R; Iida S
[Ad] Endereço:Department of Hematology and Oncology and.
[Ti] Título:Cyclin-dependent kinase 9 is a novel specific molecular target in adult T-cell leukemia/lymphoma.
[So] Source:Blood;130(9):1114-1124, 2017 Aug 31.
[Is] ISSN:1528-0020
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Cyclin-dependent kinase 9 (CDK9), a subunit of the positive transcription elongation factor b (P-TEFb) complex, regulates gene transcription elongation by phosphorylating the C-terminal domain (CTD) of RNA polymerase II (RNAPII). The deregulation of CDK9/P-TEFb has important implications for many cancer types. BAY 1143572 is a novel and highly selective CDK9/P-TEFb inhibitor currently being investigated in phase 1 studies. We evaluated the therapeutic potential of BAY 1143572 in adult T-cell leukemia/lymphoma (ATL). As a result of CDK9 inhibition and subsequent inhibition of phosphorylation at serine 2 of the RNAPII CTD, BAY 1143572 decreased c-Myc and Mcl-1 levels in ATL-derived or human T-cell lymphotropic virus type-1 (HTLV-1)-transformed lines and primary ATL cells tested, leading to their growth inhibition and apoptosis. Median inhibitory concentrations for BAY 1143572 in ATL-derived or HTLV-1-transformed lines (n = 8), primary ATL cells (n = 11), and CD4 cells from healthy volunteers (n = 5) were 0.535, 0.30, and 0.36 µM, respectively. Next, NOG mice were used as recipients of tumor cells from an ATL patient. BAY 1143572-treated ATL-bearing mice (once daily 12.5 mg/kg oral application) demonstrated significantly decreased ATL cell infiltration of the liver and bone marrow, as well as decreased human soluble interleukin-2 receptor levels in serum (reflecting the ATL tumor burden), compared with untreated mice (n = 8 for both). BAY 1143572-treated ATL-bearing mice demonstrated significantly prolonged survival compared with untreated ATL-bearing mice (n = 7 for both). Collectively, this study indicates that BAY 1143572 showed strong potential as a novel treatment of ATL.
[Mh] Termos MeSH primário: Quinase 9 Dependente de Ciclina/antagonistas & inibidores
Leucemia-Linfoma de Células T do Adulto/enzimologia
Terapia de Alvo Molecular
[Mh] Termos MeSH secundário: Animais
Apoptose/efeitos dos fármacos
Medula Óssea/efeitos dos fármacos
Medula Óssea/patologia
Linhagem Celular Transformada
Linhagem Celular Tumoral
Proliferação Celular/efeitos dos fármacos
Separação Celular
Quinase 9 Dependente de Ciclina/metabolismo
Vírus 1 Linfotrópico T Humano/fisiologia
Seres Humanos
Estimativa de Kaplan-Meier
Leucemia-Linfoma de Células T do Adulto/tratamento farmacológico
Leucemia-Linfoma de Células T do Adulto/patologia
Fígado/efeitos dos fármacos
Fígado/patologia
Camundongos
Inibidores de Proteínas Quinases/farmacocinética
Inibidores de Proteínas Quinases/farmacologia
Receptores de Interleucina-2/metabolismo
Transdução de Sinais/efeitos dos fármacos
Solubilidade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Protein Kinase Inhibitors); 0 (Receptors, Interleukin-2); EC 2.7.11.22 (Cyclin-Dependent Kinase 9)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170925
[Lr] Data última revisão:
170925
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170625
[St] Status:MEDLINE
[do] DOI:10.1182/blood-2016-09-741983


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[PMID]:28645874
[Au] Autor:Schwedhelm K; Thorpe J; Murray SA; Gavin M; Speake C; Greenbaum C; Cerosaletti K; Buckner J; Long SA
[Ad] Endereço:Translational Research Program, Benaroya Research Institute, Seattle, WA, USA.
[Ti] Título:Attenuated IL-2R signaling in CD4 memory T cells of T1D subjects is intrinsic and dependent on activation state.
[So] Source:Clin Immunol;181:67-74, 2017 Aug.
[Is] ISSN:1521-7035
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The IL-2/IL-2R pathway is implicated in type 1 diabetes (T1D). While its role in regulatory T cell (Treg) biology is well characterized, mechanisms that influence IL-2 responses in effector T cells (Teff) are less well understood. We compared IL-2 responses in 95 healthy control and 98 T1D subjects. In T1D, low IL-2 responsiveness was most pronounced in memory Teff. Unlike Treg, CD25 expression did not influence the Teff responses. Reduced IL-2 responses in memory Teff were not rescued by resting, remained lower after activation and proliferation, and were absent in type 2 diabetes. Comparing basal IL-2 responses in resting versus activated cells, memory Teff displayed lower, but more sustained, responses to IL-2 overtime. These results suggest that T1D-associated defects in the Teff compartment are due to intrinsic factors related to activation. Evaluation of both Teff and Treg IL-2R signaling defects in T1D subjects may inform selection of therapies.
[Mh] Termos MeSH primário: Linfócitos T CD4-Positivos/imunologia
Diabetes Mellitus Tipo 1/imunologia
Interleucina-2/imunologia
Receptores de Interleucina-2/imunologia
Subpopulações de Linfócitos T/imunologia
[Mh] Termos MeSH secundário: Adolescente
Adulto
Estudos de Casos e Controles
Diabetes Mellitus Tipo 2/imunologia
Feminino
Seres Humanos
Técnicas In Vitro
Ativação Linfocitária/imunologia
Masculino
Meia-Idade
Receptores de Antígenos de Linfócitos T/imunologia
Transdução de Sinais
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (IL2 protein, human); 0 (Interleukin-2); 0 (Receptors, Antigen, T-Cell); 0 (Receptors, Interleukin-2)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170828
[Lr] Data última revisão:
170828
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170625
[St] Status:MEDLINE


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[PMID]:28556984
[Au] Autor:Flynn MJ; Hartley JA
[Ad] Endereço:UCL Cancer Institute, London, UK.
[Ti] Título:The emerging role of anti-CD25 directed therapies as both immune modulators and targeted agents in cancer.
[So] Source:Br J Haematol;179(1):20-35, 2017 Oct.
[Is] ISSN:1365-2141
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:CD25 (also termed IL2RA) forms one component of the high-affinity heterotrimeric interleukin 2 (IL2) receptor on activated T cells. Its affinity for IL2 and cellular function are tightly regulated and vary in different cell types. The high frequency of CD25 on the surface of many different haematological tumour cells is now well established and, apart from its prognostic significance, CD25 may be present on leukaemic stem cells and enable oncogenic signalling pathways in leukaemic cells. Additionally, high CD25 expression in activated circulating immune cells and Tregs is a factor that has already been exploited by IL2 immunotherapies for treatment of tumours and autoimmune disease. The relative clinical safety and efficacy of administering anti-CD25 radioimmunoconjugates and immunotoxins in various haematological tumour indications has been established and clinical trials of a novel CD25-directed antibody drug conjugate are underway.
[Mh] Termos MeSH primário: Anticorpos Monoclonais/uso terapêutico
Fatores Imunológicos/uso terapêutico
Imunomodulação/efeitos dos fármacos
Subunidade alfa de Receptor de Interleucina-2/antagonistas & inibidores
Terapia de Alvo Molecular
Neoplasias/tratamento farmacológico
Neoplasias/imunologia
[Mh] Termos MeSH secundário: Anticorpos Monoclonais/farmacologia
Regulação da Expressão Gênica/efeitos dos fármacos
Seres Humanos
Fatores Imunológicos/farmacologia
Interleucina-2/metabolismo
Subunidade alfa de Receptor de Interleucina-2/genética
Subunidade alfa de Receptor de Interleucina-2/imunologia
Subunidade alfa de Receptor de Interleucina-2/metabolismo
Neoplasias/genética
Neoplasias/metabolismo
Receptores de Interleucina-2/metabolismo
Transdução de Sinais/efeitos dos fármacos
Linfócitos T Reguladores/efeitos dos fármacos
Linfócitos T Reguladores/imunologia
Linfócitos T Reguladores/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antibodies, Monoclonal); 0 (Immunologic Factors); 0 (Interleukin-2); 0 (Interleukin-2 Receptor alpha Subunit); 0 (Receptors, Interleukin-2)
[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:170531
[St] Status:MEDLINE
[do] DOI:10.1111/bjh.14770


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[PMID]:28544905
[Au] Autor:Dlouhy I; Filella X; Rovira J; Magnano L; Rivas-Delgado A; Baumann T; Martínez-Trillos A; Balagué O; Martínez A; González-Farre B; Karube K; Gine E; Delgado J; Campo E; López-Guillermo A
[Ad] Endereço:Department of Hematology, Hospital Clinic, Villarroel St. 170, 08036 Barcelona, Spain. Electronic address: idlouhy@clinic.ub.es.
[Ti] Título:High serum levels of soluble interleukin-2 receptor (sIL2-R), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF) are associated with adverse clinical features and predict poor outcome in diffuse large B-cell lymphoma.
[So] Source:Leuk Res;59:20-25, 2017 Aug.
[Is] ISSN:1873-5835
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Diffuse large B-cell lymphoma (DLBCL) is an aggressive lymphoma with heterogeneous outcomes. To improve accuracy of the international prognostic index score, new biological variables are being investigated. The aim of this study was to determine the prognostic significance of serum levels of different cytokines, namely soluble interleukin-2 receptor (sIL2-R), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF). We analyzed 197 de novo DLBCL patients (91 M/106 F; median age 66 years) treated with immunochemotherapy in a single institution. Serum cytokine determination was performed with ELISA, using the upper normal values as cut-offs. sIL-2R, IL-6 and TNF were elevated in 133, 130 and 144 cases, respectively. Elevation of each of these cytokines correlated with worse performance status, presence of B symptoms, advanced stage, elevated LDH and ß2-microglobulin (P<0.03) and lower complete remission rate (P<0.001). Elevated levels of serum sIL-2R and TNF were significantly associated with shorter progression-free (PFS) and overall survival (OS), while elevated IL-6 only with shorter PFS. Early death (<4months from diagnosis) strongly correlated with elevated cytokines. Determination of serum cytokines levels is simple and adds information regarding risk of early death, response to therapy, and outcome.
[Mh] Termos MeSH primário: Interleucina-6/sangue
Linfoma Difuso de Grandes Células B/diagnóstico
Receptores de Interleucina-2/sangue
Fator de Necrose Tumoral alfa/sangue
[Mh] Termos MeSH secundário: Idoso
Citocinas/sangue
Intervalo Livre de Doença
Feminino
Seres Humanos
Linfoma Difuso de Grandes Células B/sangue
Linfoma Difuso de Grandes Células B/mortalidade
Masculino
Meia-Idade
Prognóstico
Indução de Remissão
Taxa de Sobrevida
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cytokines); 0 (Interleukin-6); 0 (Receptors, Interleukin-2); 0 (Tumor Necrosis Factor-alpha)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171003
[Lr] Data última revisão:
171003
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170526
[St] Status:MEDLINE


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[PMID]:28497365
[Au] Autor:Lin M; Park S; Hayden A; Giustini D; Trinkaus M; Pudek M; Mattman A; Schneider M; Chen LYC
[Ad] Endereço:Division of Hematology, Department of Medicine, University of British Columbia, 2775 Laurel St, 10th Floor Room 10245, Vancouver, BC, V5Z 1M9, Canada.
[Ti] Título:Clinical utility of soluble interleukin-2 receptor in hemophagocytic syndromes: a systematic scoping review.
[So] Source:Ann Hematol;96(8):1241-1251, 2017 Aug.
[Is] ISSN:1432-0584
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:The serum-soluble interleukin-2 receptor (sIL-2r) level is considered an important diagnostic test and disease marker in hemophagocytic syndromes/hemophagocytic lymphohistiocytosis (HPS/HLH). However, this cytokine receptor is rarely measured in clinical practice and has been excluded from recent diagnostic/classification criteria such as the HScore and macrophage activation syndrome (MAS) 16. We performed a systematic scoping review of 64 articles (1975-2016) examining the clinical utility of sIL-2r in HPS/HLH. Twenty-two articles describe sIL-2r as a sensitive diagnostic marker for HLH, but only three distinct datasets actually address sensitivity. The original HLH-2004 Guidelines reported sensitivity of 93% and specificity of 100% for sIL-2r ≥ 2400, based on a pediatric dataset (n = 152) which is published for the first time in this review. Two pediatric studies reported sensitivity of 89% for sIL-2r ≥ 2400 in diagnosis of MAS complicating juvenile idiopathic arthritis (JIA) (n = 27) and 88% for secondary HLH in acute liver failure (n = 9). Twenty articles described sIL-2r as a dynamic marker of disease activity that falls with response to treatment, and 15 described high initial sIL-2r levels >10,000 U/mL as a poor prognostic marker. The ability of sIL-2r to distinguish between subtypes of HPS/HLH was inconsistent. This review confirms the importance of soluble IL-2r as a diagnostic and disease marker in HPS/HLH, but also reveals the need for more primary data about its performance characteristics, particularly in adults. More emphasis should be made in including this simple, inexpensive test in clinical practice and studies of HPS/HLH.
[Mh] Termos MeSH primário: Biomarcadores/sangue
Linfo-Histiocitose Hemofagocítica/sangue
Linfo-Histiocitose Hemofagocítica/diagnóstico
Receptores de Interleucina-2/sangue
[Mh] Termos MeSH secundário: Criança
Pré-Escolar
Seres Humanos
Linfo-Histiocitose Hemofagocítica/terapia
Síndrome de Ativação Macrofágica/sangue
Síndrome de Ativação Macrofágica/diagnóstico
Prognóstico
Sensibilidade e Especificidade
Solubilidade
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Biomarkers); 0 (Receptors, Interleukin-2)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170804
[Lr] Data última revisão:
170804
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170513
[St] Status:MEDLINE
[do] DOI:10.1007/s00277-017-2993-y


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[PMID]:28447161
[Au] Autor:Budde H; Papert S; Maas JH; Reichardt HM; Wulf G; Hasenkamp J; Riggert J; Legler TJ
[Ad] Endereço:Department of Transfusion Medicine, University Medical Center Göttingen, Robert-Koch-Str. 40, 37075, Göttingen, Germany. holger.budde@med.uni-goettingen.de.
[Ti] Título:Prediction of graft-versus-host disease: a biomarker panel based on lymphocytes and cytokines.
[So] Source:Ann Hematol;96(7):1127-1133, 2017 Jul.
[Is] ISSN:1432-0584
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Graft-versus-host disease (GvHD) still belongs to the major challenges after allogeneic hematopoietic stem cell transplantation (HSCT). Immune-suppressive therapy against GvHD is a double-edged sword due to risk of infections and relapse. The ability to adapt prophylactic treatment according to the probability of severe GvHD would be an essential advantage for the patients. We analyzed different biomarkers for their potential to predict the development of GvHD in 28 patients who underwent allogeneic HSCT. Blood was taken once directly after hematopoietic engraftment. In this study, patients were monitored for 12 months after HSCT for the occurrence of acute GvHD or acute/chronic GvHD overlap syndrome. Soluble IL-2 receptor and CD4/CD8 T cell ratio were independently associated with the occurrence of GvHD in the observation period. However, the largest area under the receiver operating characteristic curve with 0.90 was observed when a 5-parameter biomarker score based on CD4 T cells, CD8 T cells, CD19 CD21 precursor B cells, CD4/CD8 T cell ratio, and soluble IL-2 receptor was used to predict GvHD. In addition, CD8 T cell levels above 2.3% of all mononuclear cells after engraftment may predict relapse-free survival at least for 12 months. In summary, we found a new biomarker panel for prediction of GvHD which is featured by established laboratory assays and high statistical significance. In order to introduce the biomarker panel into routine clinical protocols, we suggest performing a larger multi-center study.
[Mh] Termos MeSH primário: Biomarcadores/metabolismo
Citocinas/metabolismo
Doença Enxerto-Hospedeiro/diagnóstico
Linfócitos/metabolismo
[Mh] Termos MeSH secundário: Adulto
Idoso
Análise de Variância
Biomarcadores/sangue
Relação CD4-CD8
Linfócitos T CD8-Positivos/metabolismo
Citocinas/sangue
Feminino
Doença Enxerto-Hospedeiro/etiologia
Doença Enxerto-Hospedeiro/metabolismo
Transplante de Células-Tronco Hematopoéticas/efeitos adversos
Transplante de Células-Tronco Hematopoéticas/métodos
Seres Humanos
Estimativa de Kaplan-Meier
Contagem de Linfócitos
Masculino
Meia-Idade
Valor Preditivo dos Testes
Prognóstico
Estudos Prospectivos
Receptores de Interleucina-2/sangue
Receptores de Interleucina-2/metabolismo
Fatores de Tempo
Transplante Homólogo
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; OBSERVATIONAL STUDY
[Nm] Nome de substância:
0 (Biomarkers); 0 (Cytokines); 0 (Receptors, Interleukin-2)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170804
[Lr] Data última revisão:
170804
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170428
[St] Status:MEDLINE
[do] DOI:10.1007/s00277-017-2999-5


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[PMID]:28413914
[Au] Autor:Umino K; Fujiwara SI; Ikeda T; Toda Y; Ito S; Mashima K; Minakata D; Nakano H; Yamasaki R; Kawasaki Y; Sugimoto M; Yamamoto C; Ashizawa M; Hatano K; Sato K; Oh I; Ohmine K; Muroi K; Kanda Y
[Ad] Endereço:a Division of Hematology, Department of Medicine , Jichi Medical University , Tochigi , Japan.
[Ti] Título:Prognostic value of the soluble interleukin-2 receptor level after patients with follicular lymphoma achieve a response to R-CHOP.
[So] Source:Hematology;22(9):521-526, 2017 Oct.
[Is] ISSN:1607-8454
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:OBJECTIVES: Follicular lymphoma (FL) is a clinically and biologically heterogeneous disease. Therefore, it is important to identify factors that can predict its clinical outcome. METHODS: We retrospectively evaluated the usefulness of soluble interleukin-2 receptor (sIL-2R) levels after R-CHOP (posttreatment sIL-2R) in 72 patients with newly diagnosed FL who had either a complete response (CR) or partial response. With the use of a recursive partitioning analysis, we determined the cut-off values of post- and pretreatment sIL-2R levels that were associated with disease progression, which corresponded to 486.5 and 5405 U/mL, respectively. RESULTS: The high posttreatment sIL-2R group showed a significantly inferior progression-free survival (PFS) compared to the low posttreatment sIL-2R group in all patients (3-year PFS 52.6% vs. 77.4%, P = 0.003), and in patients with CR (3-year PFS 57.1% vs. 82.1%, P = 0.034). Although a multivariate analysis showed that pretreatment sIL-2R, but not posttreatment sIL-2R, was an independently significant predictive factor for disease progression, among patients with low pretreatment sIL-2R levels, those with high posttreatment sIL-2R levels tended to have inferior PFS. There was a significant trend in PFS among the high pretreatment sIL-2R group, the low pre- and high posttreatment sIL-2R group, and the low pre- and low posttreatment sIL-2R group (P < 0.001). CONCLUSION: Among patients with a low pretreatment sIL-2R level who exhibited a positive response to R-CHOP, the posttreatment sIL-2R level may help to identify those with a poor prognosis.
[Mh] Termos MeSH primário: Linfoma Folicular/sangue
Linfoma Folicular/mortalidade
Receptores de Interleucina-2/sangue
[Mh] Termos MeSH secundário: Adulto
Idoso
Anticorpos Monoclonais Murinos
Protocolos de Quimioterapia Combinada Antineoplásica
Biomarcadores
Ciclofosfamida
Doxorrubicina
Feminino
Seres Humanos
Estimativa de Kaplan-Meier
Linfoma Folicular/diagnóstico
Linfoma Folicular/tratamento farmacológico
Masculino
Meia-Idade
Gradação de Tumores
Estadiamento de Neoplasias
Prednisona
Prognóstico
Modelos de Riscos Proporcionais
Estudos Retrospectivos
Resultado do Tratamento
Vincristina
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Monoclonal, Murine-Derived); 0 (Biomarkers); 0 (R-CHOP protocol); 0 (Receptors, Interleukin-2); 5J49Q6B70F (Vincristine); 80168379AG (Doxorubicin); 8N3DW7272P (Cyclophosphamide); VB0R961HZT (Prednisone)
[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:170418
[St] Status:MEDLINE
[do] DOI:10.1080/10245332.2017.1312204


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[PMID]:28383112
[Au] Autor:Binder M; O'Byrne MM; Maurer MJ; Ansell S; Feldman AL; Cerhan J; Novak A; Porrata LF; Markovic S; Link BK; Witzig TE
[Ad] Endereço:Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota.
[Ti] Título:Associations between elevated pre-treatment serum cytokines and peripheral blood cellular markers of immunosuppression in patients with lymphoma.
[So] Source:Am J Hematol;92(8):752-758, 2017 Aug.
[Is] ISSN:1096-8652
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Higher ratios of the pre-treatment peripheral blood absolute lymphocyte (ALC) to absolute monocyte counts (AMC) are associated with improved outcomes in lymphoma. Conversely, elevated pre-treatment serum cytokines are associated with inferior outcomes. The relationship between pre-treatment serum cytokines and ALC/AMC ratios remains unknown. We studied twelve serum cytokines and the ALC/AMC ratios in 390 patients with untreated diffuse large B-cell, follicular, mantle cell, T-cell, and Hodgkin lymphoma. Different pre-treatment serum cytokine concentrations correlated with ALC, AMC, and ALC/AMC ratios depending on the lymphoma type. In the entire cohort (n = 390) lower ALC/AMC ratios modestly correlated with higher IL-2R (r = -0.36), IL-12 (r = -0.17), IP-10 (r = -0.23), and MIG (r = -0.32) concentrations (p < 0.001). Elevated IL-2R was independently associated with suppressed ALC (OR 2.69, 95% CI 1.77-4.07, p < 0.001), elevated AMC (OR 2.05, 95% CI 1.34-3.14, p < 0.001), and suppressed ALC/AMC ratios (OR 3.51, 95% CI 2.31-5.34, p < 0.001). Both elevated IL-2R (HR 2.27, 95% CI 1.48-3.49, p < 0.001) and suppressed ALC/AMC ratios (HR 1.53, 95% CI 1.03-2.28, p = 0.037) were independently associated with inferior overall survival. These data support the notion that elevated serum cytokines are immunosuppressive and provide further rationale to target the tumor microenvironment for therapeutic benefit.
[Mh] Termos MeSH primário: Biomarcadores
Células Sanguíneas/imunologia
Células Sanguíneas/metabolismo
Citocinas/sangue
Linfoma/imunologia
Linfoma/metabolismo
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Terapia Combinada
Feminino
Seres Humanos
Estimativa de Kaplan-Meier
Contagem de Leucócitos
Linfócitos/patologia
Linfoma/diagnóstico
Linfoma/terapia
Masculino
Meia-Idade
Monócitos/patologia
Estadiamento de Neoplasias
Prognóstico
Receptores de Interleucina-2/metabolismo
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers); 0 (Cytokines); 0 (Receptors, Interleukin-2)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171121
[Lr] Data última revisão:
171121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170407
[St] Status:MEDLINE
[do] DOI:10.1002/ajh.24758


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[PMID]:28381754
[Au] Autor:Fukushima M; Okoshi Y; Fukazawa K; Koshino M; Ishiguro S; Mitsuhashi S; Saitoh H; Iijima T; Kojima H; Hori M
[Ad] Endereço:Department of Hematology, Ibaraki Prefectural Central Hospital, Japan.
[Ti] Título:Lymphoplasmacytic Lymphoma Presenting with Diarrhea and Joint Pain Which was Successfully Diagnosed by an MYD88 Mutation Analysis.
[So] Source:Intern Med;56(7):847-851, 2017.
[Is] ISSN:1349-7235
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:A 55-year-old man presented to our department with diarrhea, weight loss, fatigability, and polyarthralgia. Blood tests revealed elevated soluble interleukin-2 receptor levels and IgG-type M protein positivity, without any findings that were suggestive of collagen disease. After computed tomography (CT) detected enlarged lymph nodes in the abdominal para-aortic region, lymphoma was suspected. CT-guided needle biopsy of the lymph node did not help to achieve a definitive diagnosis; however, a bone marrow test showed the pathological features of B-cell lymphoma. A genetic examination detected a MYD88 L265P mutation; the mutation analysis was valuable in diagnosing lymphoplasmacytic lymphoma in a IgM-type M protein-negative patient.
[Mh] Termos MeSH primário: Fator 88 de Diferenciação Mieloide/genética
Macroglobulinemia de Waldenstrom/diagnóstico
Macroglobulinemia de Waldenstrom/genética
[Mh] Termos MeSH secundário: Medula Óssea/patologia
Análise Mutacional de DNA
Diagnóstico Diferencial
Glicoproteínas/biossíntese
Seres Humanos
Linfonodos/patologia
Masculino
Meia-Idade
Mutação
Receptores de Interleucina-2/biossíntese
Macroglobulinemia de Waldenstrom/patologia
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Glycoproteins); 0 (Myeloid Differentiation Factor 88); 0 (Receptors, Interleukin-2); 0 (protein M (glycoprotein))
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170609
[Lr] Data última revisão:
170609
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170407
[St] Status:MEDLINE
[do] DOI:10.2169/internalmedicine.56.7340



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