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[PMID]:29362889
[Au] Autor:Gaudio F; Tamma R; Ingravallo G; Perrone T; Laddaga FE; De Candia M; Maiorano E; Ribatti D; Specchia G
[Ad] Endereço:Department of Emergency and Organ Transplantation (D.E.T.O.), Hematology Section, University of Bari, Bari, Italy. fragaudio@alice.it.
[Ti] Título:Computer-driven quantitative image analysis in the assessment of tumor cell and T cell features in diffuse large B cell lymphomas.
[So] Source:Ann Hematol;97(4):663-668, 2018 Apr.
[Is] ISSN:1432-0584
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Diffuse large B cell lymphoma (DLBCL) is recognized as the most common non-Hodgkin lymphoma subtype. Advanced high-resolution digital scans of pathology slides have enabled the development of computer-based image analysis algorithms that may assist pathologists in quantifying immunohistochemical stains. In this retrospective study, we reviewed data from 29 patients affected by DLBCL. In order to evaluate the number of tumor cells and microenvironment T cells, we performed an analysis of CD20, Ki67, and CD3 counts, assessed with the Positive Pixel Count algorithm embedded in the Aperio ImageScope software. A lower tumor cell count was observed in patients with a non-germinal center immunophenotype, high LDH, splenomegaly and an IPI ≥ 3. A lower number of CD3 was observed in patients with bulky disease, an IPI ≥ 3 and disease stage 3-4. Overall, these data confirm that quantitative analysis of the tumor cells and of the tumor microenvironment by means of computer-driven quantitative image analysis may add new information in DLBCL diagnosis.
[Mh] Termos MeSH primário: Linfócitos B/patologia
Interpretação de Imagem Assistida por Computador
Linfonodos/diagnóstico por imagem
Linfoma Difuso de Grandes Células B/diagnóstico por imagem
Linfócitos T/patologia
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Algoritmos
Antígenos CD20/metabolismo
Linfócitos B/imunologia
Linfócitos B/metabolismo
Complexo CD3/metabolismo
Feminino
Centro Germinativo/imunologia
Centro Germinativo/metabolismo
Centro Germinativo/patologia
Seres Humanos
Imuno-Histoquímica
Antígeno Ki-67/metabolismo
Linfonodos/imunologia
Linfonodos/metabolismo
Linfonodos/patologia
Linfoma Difuso de Grandes Células B/imunologia
Linfoma Difuso de Grandes Células B/metabolismo
Linfoma Difuso de Grandes Células B/patologia
Masculino
Meia-Idade
Estadiamento de Neoplasias
Prognóstico
Estudos Retrospectivos
Linfócitos T/imunologia
Linfócitos T/metabolismo
Microambiente Tumoral
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, CD20); 0 (CD3 Complex); 0 (Ki-67 Antigen)
[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:180125
[St] Status:MEDLINE
[do] DOI:10.1007/s00277-017-3212-6


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[PMID]:28922789
[Au] Autor:Mlecnik B; Van den Eynde M; Bindea G; Church SE; Vasaturo A; Fredriksen T; Lafontaine L; Haicheur N; Marliot F; Debetancourt D; Pairet G; Jouret-Mourin A; Gigot JF; Hubert C; Danse E; Dragean C; Carrasco J; Humblet Y; Valge-Archer V; Berger A; Pagès F; Machiels JP; Galon J
[Ad] Endereço:Laboratory of Integrative Cancer Immunology, INSERM, UMRS1138, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, UMRS1138, Paris, France; Sorbonne Universités, UPMC Univ Paris 06, UMRS1138, Centre de Recherche des Cordeliers, Paris, France; Inovarion, Paris, France; Department of Medic
[Ti] Título:Comprehensive Intrametastatic Immune Quantification and Major Impact of Immunoscore on Survival.
[So] Source:J Natl Cancer Inst;110(1), 2018 Jan 01.
[Is] ISSN:1460-2105
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Background: This study assesses how the metastatic immune landscape is impacting the response to treatment and the outcome of colorectal cancer (CRC) patients. Methods: Complete curative resection of metastases (n = 441) was performed for two patient cohorts (n = 153). Immune densities were quantified in the center and invasive margin of all metastases. Immunoscore and T and B cell (TB) score were analyzed in relation to radiological and pathological responses and patient's disease-free (DFS) and overall survival (OS) using multivariable Cox proportional hazards models. All statistical tests were two-sided. Results: The spatial distribution of immune cells within metastases was nonuniform. Patients, as well as metastases of the same patient, had variable immune infiltrates and response to therapy. A beneficial response was statistically significantly associated with increased immune densities. Among all metastases, Immunoscore (I) and TB score evaluated in the least immune-infiltrated metastases were the strongest predictors for DFS and OS (five-year follow-up, Immunoscore: I 3-4: DFS rate = 27.9%, 95% CI = 15.2 to 51.3; vs I 0-1-2: DFS rate = 12.3%, 95% CI = 4.9 to 30.6; HR = 0.45, 95% CI = 0.28 to 0.70, P = .02; I 3-4: OS rate = 64.6%, 95% CI = 46.6 to 89.6; vs I 0-1-2: OS rate = 32.5%, 95% CI = 17.2 to 61.4; HR = 0.32, 95% CI = 0.15 to 0.66, P = .001, C-index = 65.9%; five-year follow-up, TB score: TB 3-4: DFS rate = 25.7%, 95% CI = 14.2 to 46.6; vs TB 0-1-2: DFS rate = 5.0%, 95% CI = 0.8 to 32.4; HR = 0.36, 95% CI = 0.22 to 0.57, P < .001; TB 3-4: OS rate = 63.7%, 95% CI = 46.4 to 87.5; vs TB 0-1-2: OS rate: 21.4%, 95% CI = 9.2 to 49.8; HR = 0.25, 95% CI = 0.12 to 0.51, P < .001, C-index = 67.8%). High TB score and Immunoscore patients had a median survival of 70.5 months, while low patients survived only 25.1 to 38.3 months. Nonresponding patients with high-immune infiltrates had prolonged DFS (HR = 0.28, 95% CI = 0.15 to 0.52, P = .001) and OS (HR = 0.25, 95% CI = 0.1 to 0.62, P = .001). The immune parameters remained the only statistically significant prognostic factor associated with DFS and OS in multivariable analysis (P < .001), while response to treatment was not. Conclusions: Response to treatment and prolonged survival of metastatic CRC patients were statistically significantly associated with high-immune densities quantified into the least immune-infiltrated metastasis.
[Mh] Termos MeSH primário: Linfócitos B
Neoplasias Colorretais/imunologia
Neoplasias Hepáticas/imunologia
Neoplasias Pulmonares/imunologia
Linfócitos do Interstício Tumoral
Linfócitos T
[Mh] Termos MeSH secundário: Idoso
Antígenos CD20/análise
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Linfócitos B/química
Complexo CD3/análise
Linfócitos T CD8-Positivos
Quimioterapia Adjuvante
Neoplasias Colorretais/patologia
Neoplasias Colorretais/terapia
Intervalo Livre de Doença
Seguimentos
Fatores de Transcrição Forkhead/análise
Hepatectomia
Seres Humanos
Antígenos Comuns de Leucócito/análise
Neoplasias Hepáticas/secundário
Neoplasias Hepáticas/terapia
Neoplasias Pulmonares/secundário
Neoplasias Pulmonares/terapia
Contagem de Linfócitos
Metastasectomia
Meia-Idade
Metástase Neoplásica
Pneumonectomia
Período Pré-Operatório
Critérios de Avaliação de Resposta em Tumores Sólidos
Taxa de Sobrevida
Linfócitos T/química
Microambiente Tumoral/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, CD20); 0 (CD3 Complex); 0 (FOXP3 protein, human); 0 (Forkhead Transcription Factors); EC 3.1.3.48 (Leukocyte Common Antigens)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170920
[St] Status:MEDLINE
[do] DOI:10.1093/jnci/djx123


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[PMID]:27776339
[Au] Autor:Jahn L; van der Steen DM; Hagedoorn RS; Hombrink P; Kester MG; Schoonakker MP; de Ridder D; van Veelen PA; Falkenburg JH; Heemskerk MH
[Ad] Endereço:Department of Hematology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
[Ti] Título:Generation of CD20-specific TCRs for TCR gene therapy of CD20low B-cell malignancies insusceptible to CD20-targeting antibodies.
[So] Source:Oncotarget;7(47):77021-77037, 2016 Nov 22.
[Is] ISSN:1949-2553
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Immunotherapy of B-cell leukemia and lymphoma with CD20-targeting monoclonal antibodies (mAbs) has demonstrated clinical efficacy. However, the emergence of unresponsive disease due to low or absent cell surface CD20 urges the need to develop additional strategies. In contrast to mAbs, T-cells via their T-cell receptor (TCR) can recognize not only extracellular but also intracellular antigens in the context of HLA molecules. We hypothesized that T-cells equipped with high affinity CD20-targeting TCRs would be able to recognize B-cell malignancies even in the absence of extracellular CD20. We isolated CD8+ T-cell clones binding to peptide-MHC-tetramers composed of HLA-A*02:01 and CD20-derived peptide SLFLGILSV (CD20SLF) from HLA-A*02:01neg healthy individuals to overcome tolerance towards self-antigens such as CD20. High avidity T-cell clones were identified that readily recognized and lysed primary HLA-A2pos B-cell leukemia and lymphoma in the absence of reactivity against CD20-negative but HLA-A2pos healthy hematopoietic and nonhematopoietic cells. The T-cell clone with highest avidity efficiently lysed malignant cell-lines that had insufficient extracellular CD20 to be targeted by CD20 mAbs. Transfer of this TCR installed potent CD20-specificity onto recipient T-cells and led to lysis of CD20low malignant cell-lines. Moreover, our approach facilitates the generation of an off-the-shelf TCR library with broad applicability by targeting various HLA alleles. Using the same methodology, we isolated a T-cell clone that efficiently lysed primary HLA-B*07:02pos B-cell malignancies by targeting another CD20-derived peptide. TCR gene transfer of high affinity CD20-specific TCRs can be a valuable addition to current treatment options for patients suffering from CD20low B-cell malignancies.
[Mh] Termos MeSH primário: Antígenos CD20/genética
Leucemia de Células B/terapia
Linfoma de Células B/terapia
Receptores de Antígenos de Linfócitos T/genética
[Mh] Termos MeSH secundário: Antígenos CD20/imunologia
Antígenos CD20/metabolismo
Linfócitos T CD8-Positivos/imunologia
Terapia Genética
Antígeno HLA-A2/imunologia
Seres Humanos
Células K562
Leucemia de Células B/genética
Leucemia de Células B/imunologia
Linfoma de Células B/genética
Linfoma de Células B/imunologia
Receptores de Antígenos de Linfócitos T/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, CD20); 0 (HLA-A2 Antigen); 0 (Receptors, Antigen, T-Cell)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180212
[Lr] Data última revisão:
180212
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161025
[St] Status:MEDLINE
[do] DOI:10.18632/oncotarget.12778


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[PMID]:29325249
[Au] Autor:Liu C; Li X; Li H; Gong QX; Li Y; Wang Z; Zhang ZH
[Ad] Endereço:Department of Pathology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
[Ti] Título:[Clinicopathologic features of primary hepatic marginal zone lymphoma of mucosa-associated lymphoid tissue and hepatic pseudolymphoma].
[So] Source:Zhonghua Bing Li Xue Za Zhi;47(1):39-44, 2018 Jan 08.
[Is] ISSN:0529-5807
[Cp] País de publicação:China
[La] Idioma:chi
[Ab] Resumo:To study the clinicopathological features of primary hepatic extranodal marginal zone lymphoma of mucosa associated lymphoid tissue (MALT lymphoma) and hepatic pseudolymphoma, and to discuss their differential diagnosis, treatment and prognosis. Three primary hepatic MALT lymphomas and two hepatic pseudolymphomas collected from January 2012 to March 2017 in the First Affiliated Hospital of Nanjing Medical University were evaluated by HE and immunohistochemistry(IHC), in-situ hybridization and immunoglobulin (Ig) gene rearrangement detection, and the relevant literature reviewed. In the three MALT lymphomas, tumor cells infiltrated the portal areas with nodular pattern, and invaded the surrounding normal liver with serpiginous configuration and formation of confluent sheets. A number of bile ducts were entrapped within the lesions, and showed lymphoepithelial lesion. Reactive lymphoid follicles were present and surrounded by tumor cells, consisting of predominantly centrocyte-like cells and monocytoid B cells. There were clusters of epithelioid histiocytes in one case. The tumor cells were positive for CD20, PAX5 and negative for CD5, CD23, CD10, bcl-6, and cyclin D1. In the two hepatic pseudolymphomas, the lesions presented as solitary nodules well-demarcated from the surrounding liver tissue; one case was partially encapsulated with fibrous tissue. Entrapped bile ducts were only found at the edge of the lesions without lymphoepithelial lesion. The lesions comprised of massive lymphoid proliferation consisting predominantly of reactive lymphoid follicles, but not monocytoid B-cells or atypical cells. By IHC, a mixture of B- and T-cell population was identified. A monoclonal rearrangement of the Ig gene was detected in all three MALT lymphomas but not in two pseudolymphomas. Interphase fluorescence in situ hybridiazation test for MALT1 break-apart gene was positive in two cases of MALT lymphomas and EBER was negative in all studied cases. Primary heptic MALT lymphoma and pseudolymphoma are both rare lymphoid proliferative lesions of liver. These two lesions have overlapping histological and IHC features and are top differential diagnosis to each other. A combination analysis of morphology, immunophenotype and Ig gene rearrangement is helpful to distinguish between them.
[Mh] Termos MeSH primário: Neoplasias Hepáticas/patologia
Tecido Linfoide/patologia
Linfoma de Zona Marginal Tipo Células B/patologia
Pseudolinfoma/patologia
[Mh] Termos MeSH secundário: Antígenos CD20
Linfócitos B/patologia
Diagnóstico Diferencial
Seres Humanos
Imuno-Histoquímica
Imunofenotipagem
Hibridização In Situ
Interfase
Neoplasias Hepáticas/química
Neoplasias Hepáticas/genética
Linfócitos/patologia
Tecido Linfoide/química
Linfoma de Zona Marginal Tipo Células B/química
Linfoma de Zona Marginal Tipo Células B/genética
Pseudolinfoma/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, CD20)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180202
[Lr] Data última revisão:
180202
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180112
[St] Status:MEDLINE
[do] DOI:10.3760/cma.j.issn.0529-5807.2018.01.008


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[PMID]:29325247
[Au] Autor:Zhang XY; Ma ZP; Cui WL; Pang XL; Chen R; Wang L; Zhang W; Li XX
[Ad] Endereço:Department of Pathology, the First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China.
[Ti] Título:[Impact of PRDM1 gene inactivation on C-MYC regulation in diffuse large B-cell lymphoma].
[So] Source:Zhonghua Bing Li Xue Za Zhi;47(1):25-31, 2018 Jan 08.
[Is] ISSN:0529-5807
[Cp] País de publicação:China
[La] Idioma:chi
[Ab] Resumo:To investigate the role of PRDM1 gene inactivaion in the regulation of C-MYC in diffuse large B-cell lymphoma (DLBCL), and to explore the correlation of its immunophenotype and prognosis. 100 cases paraffin-embedded DLBCL tissues were collected from January 2009 to December 2015 at the First Affiliated Hospital of Xinjiang Medical University along with 20 cases of reactive proliferative lymph nodes as control. Immunohistochemical methods were used to detect the expression of CD20, CD10, MUM1, Ki-67, bcl-6, PRDM1/Blimp1, C-MYC and PAX5 protein. The tumors were classified into two subtypes according to Hans classification.The expression of PRDM1 and C-MYC gene in tumor group and control group was detected by reverse transcription PCR (RT-PCR) and the relationship between PRDM1 and C-MYC gene was analyzed.OCI-LY1 (GCB subtype) and OCI-LY3 (non-GCB subtype) cell lines were transfected with small interfering RNA by cationic liposome reagent transfection, and the expression of C-MYC in the transfected cell lines was detected by RT-PCR and Western blot. The Kaplan-Meier method was used to analyze the prognostic significance of PRDM1/Blimp1 and C-MYC at protein and mRNA levels. There were 27 cases of GCB subtype and 73 cases of non-GCB subtype according to Hans classification. The positive expression of Blimp1 in DLBCL group and proliferative lymph nodes in control group was seen in 26(26.0%) and 20 cases(100%), respectively. There were 58 cases with high expression of PRDM1 at mRNA level, including 22 cases of GCB subtype and 36 cases non-GCB subtype, and the difference was statistically significant ( =0.004). There were differences in PRDM1 gene expression between the two immunological subtypes, serum lactate dehydrogenase (serum LDH) level, presence of B symptoms, tumor primary sites and other clinical pathological parameters, while C-MYC expression was different in gender, IPI score, and serum LDH levels. Upon PRDM1/Blimp1 gene silencing in the two cell lines, C-MYC protein and gene expression were up-regulated in the transfection group, compared with the blank control group and negative control group by reverse transcription PCR and Western blot analyses. Moreover, PRDM1 expression was significantly associated with C-MYC(χ(2)=7.648, =0.006) at mRNA level. The up-regulation of C-MYC gene expression induced by PRDM1 inactivation in DLBCL may play an important role for the development of DLBCL.PRDM1 protein and mRNA are associated with immunophenotyping and PRDM1 mRNA is a marker of poor prognosis.
[Mh] Termos MeSH primário: Inativação Gênica
Genes myc
Linfoma Difuso de Grandes Células B/genética
Fator 1 de Ligação ao Domínio I Regulador Positivo/genética
[Mh] Termos MeSH secundário: Antígenos CD20/metabolismo
Linhagem Celular Tumoral
Regulação Neoplásica da Expressão Gênica
Seres Humanos
Imunofenotipagem
Linfonodos/patologia
Linfoma Difuso de Grandes Células B/patologia
Fator de Transcrição PAX5/metabolismo
Fator 1 de Ligação ao Domínio I Regulador Positivo/metabolismo
Prognóstico
Proteínas Proto-Oncogênicas c-bcl-6/genética
Proteínas Proto-Oncogênicas c-bcl-6/metabolismo
Proteínas Proto-Oncogênicas c-myc/metabolismo
RNA Mensageiro/metabolismo
Proteínas Repressoras/metabolismo
Regulação para Cima
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, CD20); 0 (PAX5 Transcription Factor); 0 (PAX5 protein, human); 0 (Proto-Oncogene Proteins c-bcl-6); 0 (Proto-Oncogene Proteins c-myc); 0 (RNA, Messenger); 0 (Repressor Proteins); 138415-26-6 (PRDM1 protein, human); EC 2.1.1.- (Positive Regulatory Domain I-Binding Factor 1)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180202
[Lr] Data última revisão:
180202
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180112
[St] Status:MEDLINE
[do] DOI:10.3760/cma.j.issn.0529-5807.2018.01.006


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[PMID]:29239464
[Au] Autor:Santos MAO; Lima MM
[Ad] Endereço:Epidemiology and Cardiology Research Group, Centro Universitário Maurício de Nassau, Universidade Federal de Pernambuco, Recife, PE, Brazil.
[Ti] Título:CD20 role in pathophysiology of Hodgkin's disease.
[So] Source:Rev Assoc Med Bras (1992);63(9):810-813, 2017 Sep.
[Is] ISSN:1806-9282
[Cp] País de publicação:Brazil
[La] Idioma:eng
[Ab] Resumo:Hodgkin's lymphoma (HL) is a tumor comprising non-malignant and malignant B-cells. Classical HL expresses CD15+ and CD30+ antigens, and 20 to 40% of patients are CD20+. This antigen is a ligand free protein present in B lymphocyte cells and its function is not well known. Some studies suggest that expression of CD20 may play a major role in Hodgkin's disease pathophysiology and may affect the patients' treatment prognosis, as well as relapse and refractory response. In the past few years, development of monoclonal anti-CD20 antibodies changed drastically the treatment for non-Hodgkin lymphomas in which CD20 is expressed. HL treatment is essentially composed of radiotherapy and chemotherapy; however, monoclonal anti-CD20 antibodies applicability is not well delimitated due to lack of information about clinical outcomes with anti-CD20 monotherapy or combined drug therapy using a classic regimen, as well as about CD20 pathophysiology mechanisms in B-cells tumors. The objective of our review is to discuss CD20 function in Hodgkin's lymphoma development, its influence on disease evolution and outcomes, as well as its effects on therapeutics and patients' prognostic.
[Mh] Termos MeSH primário: Anticorpos Monoclonais Humanizados/uso terapêutico
Anticorpos Monoclonais/uso terapêutico
Antígenos CD20/fisiologia
Doença de Hodgkin/tratamento farmacológico
Doença de Hodgkin/fisiopatologia
Rituximab/uso terapêutico
[Mh] Termos MeSH secundário: Doença de Hodgkin/etiologia
Seres Humanos
Prognóstico
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antibodies, Monoclonal); 0 (Antibodies, Monoclonal, Humanized); 0 (Antigens, CD20); 4F4X42SYQ6 (Rituximab); O43472U9X8 (obinutuzumab)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180123
[Lr] Data última revisão:
180123
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171215
[St] Status:MEDLINE


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[PMID]:28855268
[Au] Autor:Haglund F; Hallström BM; Nilsson IL; Höög A; Juhlin CC; Larsson C
[Ad] Endereço:Department of Oncology-PathologyKarolinska Institutet, Cancer Center Karolinska (CCK), Karolinska University Hospital, Stockholm, Sweden Felix.Haglund@ki.se.
[Ti] Título:Inflammatory infiltrates in parathyroid tumors.
[So] Source:Eur J Endocrinol;177(6):445-453, 2017 Dec.
[Is] ISSN:1479-683X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:CONTEXT: Inflammatory infiltrates are sometimes present in solid tumors and may be coupled to clinical behavior or etiology. Infectious viruses contribute to tumorigenesis in a significant fraction of human neoplasias. OBJECTIVE: Characterize inflammatory infiltrates and possible viral transcription in primary hyperparathyroidism. DESIGN: From the period 2007 to 2016, a total of 55 parathyroid tumors (51 adenomas and 4 hyperplasias) with prominent inflammatory infiltrates were identified from more than 2000 parathyroid tumors in the pathology archives, and investigated by immunohistochemistry for CD4, CD8, CD20 and CD45 and scored as +0, +1 or +2. Clinicopathological data were compared to 142 parathyroid adenomas without histological evidence of inflammation. Transcriptome sequencing was performed for 13 parathyroid tumors (four inflammatory, 9 non-inflammatory) to identify potential viral transcripts. RESULTS: Tumors had prominent germinal center-like nodular (+2) lymphocytic infiltrates consisting of T and B lymphocytes (31%) and/or diffuse (+1-2) infiltrates of predominantly CD8+ T lymphocytes (84%). In the majority of cases with adjacent normal parathyroid tissue, the normal rim was unaffected by the inflammatory infiltrates (96%). Presence of inflammatory infiltrates was associated with higher levels of serum-PTH ( = 0.007) and oxyphilic differentiation ( = 0.002). Co-existent autoimmune disease was observed in 27% of patients with inflammatory infiltrates, which in turn was associated with oxyphilic differentiation ( = 0.041). Additionally, prescription of anti-inflammatory drugs was associated with lower serum ionized calcium ( = 0.037). CONCLUSIONS: No evidence of virus-like sequences in the parathyroid tumors could be found by transcriptome sequencing, suggesting that other factors may contribute to attract the immune system to the parathyroid tumor tissue.
[Mh] Termos MeSH primário: Adenoma/imunologia
Linfócitos B/imunologia
Linfócitos T CD4-Positivos/imunologia
Linfócitos T CD8-Positivos/imunologia
Hiperparatireoidismo Primário/imunologia
Glândulas Paratireoides/imunologia
Neoplasias das Paratireoides/imunologia
[Mh] Termos MeSH secundário: Adenoma/metabolismo
Adenoma/patologia
Adenoma/virologia
Antígenos CD20/metabolismo
Linfócitos B/metabolismo
Linfócitos B/patologia
Biomarcadores/metabolismo
Linfócitos T CD4-Positivos/metabolismo
Linfócitos T CD4-Positivos/patologia
Linfócitos T CD8-Positivos/metabolismo
Linfócitos T CD8-Positivos/patologia
Estudos de Coortes
Feminino
Seres Humanos
Hiperparatireoidismo Primário/metabolismo
Hiperparatireoidismo Primário/patologia
Hiperparatireoidismo Primário/virologia
Hiperplasia/imunologia
Hiperplasia/patologia
Imuno-Histoquímica
Antígenos Comuns de Leucócito/metabolismo
Leucócitos/imunologia
Leucócitos/metabolismo
Leucócitos/patologia
Masculino
Meia-Idade
Glândulas Paratireoides/metabolismo
Glândulas Paratireoides/patologia
Glândulas Paratireoides/virologia
Neoplasias das Paratireoides/metabolismo
Neoplasias das Paratireoides/patologia
Neoplasias das Paratireoides/virologia
RNA Viral/metabolismo
Estudos Retrospectivos
Transcrição Genética
Proteínas Virais/genética
Proteínas Virais/metabolismo
Replicação Viral
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, CD20); 0 (Biomarkers); 0 (RNA, Viral); 0 (Viral Proteins); EC 3.1.3.48 (Leukocyte Common Antigens)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170901
[St] Status:MEDLINE
[do] DOI:10.1530/EJE-17-0277


  8 / 3772 MEDLINE  
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[PMID]:28845710
[Au] Autor:Klein C; Bacac M; Umana P; Fingerle-Rowson G
[Ad] Endereço:a Roche Pharmaceutical Research & Early Development , Roche Innovation Center Zurich , Zurich , Switzerland.
[Ti] Título:Combination therapy with the type II anti-CD20 antibody obinutuzumab.
[So] Source:Expert Opin Investig Drugs;26(10):1145-1162, 2017 Oct.
[Is] ISSN:1744-7658
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: Obinutuzumab is a novel humanized type II glycoengineered anti-CD20 antibody approved for first-line treatment of chronic lymphocytic leukemia (CLL) in combination with chlorambucil and for treatment of rituximab-refractory follicular lymphoma (FL). Areas covered: We describe current preclinical and clinical evidence supporting the combination of obinutuzumab with not only chemotherapy but also novel targeted therapies for B-cell hematologic malignancies, and its application in chemoimmunotherapy. We also provide an overview of the current clinical trial landscape investigating novel combination therapies based on obinutuzumab. Expert opinion: Within the next 10 years the treatment of B-cell malignancies with obinutuzumab is expected to increasingly move towards chemotherapy-free regimens. Novel combinations of obinutuzumab will be explored with targeted therapies, antibody-drug conjugates, and/or other immunotherapeutic agents, with the aim to achieve clinically meaningful improvements in efficacy and patient safety.
[Mh] Termos MeSH primário: Anticorpos Monoclonais Humanizados/administração & dosagem
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Leucemia Linfocítica Crônica de Células B/tratamento farmacológico
[Mh] Termos MeSH secundário: Animais
Antígenos CD20/imunologia
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
Clorambucila/administração & dosagem
Seres Humanos
Leucemia Linfocítica Crônica de Células B/imunologia
Leucemia Linfocítica Crônica de Células B/patologia
Terapia de Alvo Molecular
Rituximab/administração & dosagem
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antibodies, Monoclonal, Humanized); 0 (Antigens, CD20); 18D0SL7309 (Chlorambucil); 4F4X42SYQ6 (Rituximab); O43472U9X8 (obinutuzumab)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170922
[Lr] Data última revisão:
170922
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170829
[St] Status:MEDLINE
[do] DOI:10.1080/13543784.2017.1373087


  9 / 3772 MEDLINE  
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[PMID]:28830887
[Au] Autor:Bobrowicz M; Dwojak M; Pyrzynska B; Stachura J; Muchowicz A; Berthel E; Dalla-Venezia N; Kozikowski M; Siernicka M; Miazek N; Zapala P; Domagala A; Bojarczuk K; Malenda A; Barankiewicz J; Graczyk-Jarzynka A; Zagozdzon A; Gabrysiak M; Diaz JJ; Karp M; Lech-Maranda E; Firczuk M; Giannopoulos K; Efremov DG; Laurenti L; Baatout D; Frenzel L; Malinowska A; Slabicki M; Zenz T; Zerrouqi A; Golab J; Winiarska M
[Ad] Endereço:Department of Immunology and.
[Ti] Título:HDAC6 inhibition upregulates CD20 levels and increases the efficacy of anti-CD20 monoclonal antibodies.
[So] Source:Blood;130(14):1628-1638, 2017 Oct 05.
[Is] ISSN:1528-0020
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Downregulation of CD20, a molecular target for monoclonal antibodies (mAbs), is a clinical problem leading to decreased efficacy of anti-CD20-based therapeutic regimens. The epigenetic modulation of CD20 coding gene ( ) has been proposed as a mechanism for the reduced therapeutic efficacy of anti-CD20 antibodies and confirmed with nonselective histone deacetylase inhibitors (HDACis). Because the use of pan-HDACis is associated with substantial adverse effects, the identification of particular HDAC isoforms involved in CD20 regulation seems to be of paramount importance. In this study, we demonstrate for the first time the role of HDAC6 in the regulation of CD20 levels. We show that inhibition of HDAC6 activity significantly increases CD20 levels in established B-cell tumor cell lines and primary malignant cells. Using pharmacologic and genetic approaches, we confirm that HDAC6 inhibition augments in vitro efficacy of anti-CD20 mAbs and improves survival of mice treated with rituximab. Mechanistically, we demonstrate that HDAC6 influences synthesis of CD20 protein independently of the regulation of transcription. We further demonstrate that translation of CD20 mRNA is significantly enhanced after HDAC6 inhibition, as shown by the increase of CD20 mRNA within the polysomal fraction, indicating a new role of HDAC6 in the posttranscriptional mechanism of CD20 regulation. Collectively, our findings suggest HDAC6 inhibition is a rational therapeutic strategy to be implemented in combination therapies with anti-CD20 monoclonal antibodies and open up novel avenues for the clinical use of HDAC6 inhibitors.
[Mh] Termos MeSH primário: Antígenos CD20/genética
Antineoplásicos/farmacologia
Inibidores de Histona Desacetilases/farmacologia
Histona Desacetilases/metabolismo
Leucemia Linfocítica Crônica de Células B/tratamento farmacológico
Linfoma não Hodgkin/tratamento farmacológico
Rituximab/farmacologia
[Mh] Termos MeSH secundário: Animais
Antígenos CD20/imunologia
Linfócitos B/efeitos dos fármacos
Linfócitos B/imunologia
Linfócitos B/patologia
Linhagem Celular Tumoral
Feminino
Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos
Desacetilase 6 de Histona
Seres Humanos
Leucemia Linfocítica Crônica de Células B/genética
Leucemia Linfocítica Crônica de Células B/imunologia
Leucemia Linfocítica Crônica de Células B/patologia
Linfoma não Hodgkin/genética
Linfoma não Hodgkin/imunologia
Linfoma não Hodgkin/patologia
Camundongos Endogâmicos BALB C
Camundongos SCID
RNA Mensageiro/genética
Células Tumorais Cultivadas
Regulação para Cima/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, CD20); 0 (Antineoplastic Agents); 0 (Histone Deacetylase Inhibitors); 0 (RNA, Messenger); 4F4X42SYQ6 (Rituximab); EC 3.5.1.98 (HDAC6 protein, human); EC 3.5.1.98 (Histone Deacetylase 6); EC 3.5.1.98 (Histone Deacetylases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170824
[St] Status:MEDLINE
[do] DOI:10.1182/blood-2016-08-736066


  10 / 3772 MEDLINE  
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[PMID]:28766389
[Au] Autor:Coiffier B
[Ad] Endereço:a Department of Hematology , Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud , Pierre-Bénite , France.
[Ti] Título:Pharmacokinetics, efficacy and safety of the rituximab biosimilar CT-P10.
[So] Source:Expert Rev Clin Pharmacol;10(9):923-933, 2017 Sep.
[Is] ISSN:1751-2441
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: Rituximab, an anti-CD20 monoclonal antibody, is a key therapeutic in the treatment of B cell lymphomas and rheumatoid arthritis (RA). Global rates of non-Hodgkin's lymphoma (NHL), chronic lymphocytic leukemia (CLL) and RA are increasing, with a concomitant rise in individual and overall treatment costs. As such, biosimilar development may help facilitate greater access to treatment. The rituximab biosimilar CT-P10 (Truxima®) has recently received approval in Europe and South Korea for all indications held by reference rituximab (RTX). Areas covered: Here, the unmet needs and current market in the treatment of NHL, CLL and RA are outlined, followed by a comprehensive examination of the analytical, pre-clinical and clinical data demonstrating the equivalence and similarity of CT-P10 to RTX including with respect to pharmacokinetics, efficacy, safety and immunogenicity. Expert commentary: The rising treatment costs of NHL, CLL and RA pose a challenge to constrained healthcare budgets worldwide. Biosimilars may provide an effective solution to this conundrum. CT-P10 is equivalent to RTX in terms of efficacy and pharmacokinetics, and has a similar safety and immunogenicity profile. Approved in all indications held by RTX, CT-P10 has the potential to reduce treatment costs and thereby increase patient access to rituximab therapy.
[Mh] Termos MeSH primário: Antineoplásicos/administração & dosagem
Medicamentos Biossimilares/administração & dosagem
Rituximab/administração & dosagem
[Mh] Termos MeSH secundário: Animais
Antígenos CD20/imunologia
Antineoplásicos/efeitos adversos
Antineoplásicos/farmacocinética
Antirreumáticos/administração & dosagem
Antirreumáticos/efeitos adversos
Antirreumáticos/farmacocinética
Artrite Reumatoide/tratamento farmacológico
Artrite Reumatoide/patologia
Medicamentos Biossimilares/efeitos adversos
Medicamentos Biossimilares/farmacocinética
Seres Humanos
Linfoma de Células B/tratamento farmacológico
Linfoma de Células B/patologia
Rituximab/efeitos adversos
Rituximab/farmacocinética
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antigens, CD20); 0 (Antineoplastic Agents); 0 (Antirheumatic Agents); 0 (Biosimilar Pharmaceuticals); 4F4X42SYQ6 (Rituximab)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170904
[Lr] Data última revisão:
170904
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170803
[St] Status:MEDLINE
[do] DOI:10.1080/17512433.2017.1359537



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