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1.
Biomolecules ; 11(8)2021 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-34439817

RESUMO

Epstein-Barr virus (EBV) and cytomegalovirus (CMV) are viruses globally distributed that have been associated with the development and prognosis of many pathologies, including hematological diseases. This study aimed to characterize the epidemiological profile of EBV infection and the infection-correlated hepatic manifestations in patients with hematological diseases of the northern Brazilian state of Amazonas. A total of 228 patients were serologically tested for the presence of anti-EBV and anti-CMV IgG antibodies through an enzyme-linked immunosorbent assay. The coinfection with CMV, sociodemographic and laboratory records of all patients were also assessed. The overall prevalence observed among the study population for EBV infection and EBV/CMV coinfection was 85.09% (95% CI: 0.80-0.90) and 78.51% (95% CI: 0.73-0.84), respectively. The age group 31-40 years old were more susceptible to EBV/CMV coinfection (95% CI: 1.59-93.41, p = 0.011), while young people aged 1-10 years old were less affected for both EBV infection (CI 95%; 0.66-0.91, p = 0.001) and EBV/CMV coinfection (95% CI: 0.52-0.81, p < 0.0001). High serum levels of the liver biomarker ferritin were associated with EBV infection (95% CI: 1.03-1.54, p = 0.031) and EBV/CMV coinfection (95% CI: 1.02-1.70, p = 0.038). Our findings indicated that the elevated prevalence of EBV infection is not associated with the hematological diseases or transfusion rates, but with the socioeconomic status of the study population. Also, this study suggests that the EBV infection and its coinfection with CMV are related to the increase of serum ferritin levels.


Assuntos
Anemia/epidemiologia , Anticorpos Antivirais/sangue , Infecções por Citomegalovirus/epidemiologia , Infecções por Vírus Epstein-Barr/epidemiologia , Ferritinas/sangue , Leucemia/epidemiologia , Linfoma/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia/imunologia , Anemia/patologia , Anemia/virologia , Biomarcadores/sangue , Transfusão de Sangue/estatística & dados numéricos , Brasil/epidemiologia , Criança , Pré-Escolar , Coinfecção , Citomegalovirus/crescimento & desenvolvimento , Citomegalovirus/patogenicidade , Infecções por Citomegalovirus/imunologia , Infecções por Citomegalovirus/patologia , Infecções por Citomegalovirus/virologia , Infecções por Vírus Epstein-Barr/imunologia , Infecções por Vírus Epstein-Barr/patologia , Infecções por Vírus Epstein-Barr/virologia , Feminino , Herpesvirus Humano 4/crescimento & desenvolvimento , Herpesvirus Humano 4/patogenicidade , Humanos , Imunoglobulina G/sangue , Lactente , Recém-Nascido , Leucemia/imunologia , Leucemia/patologia , Leucemia/virologia , Fígado/imunologia , Fígado/patologia , Fígado/virologia , Linfoma/imunologia , Linfoma/patologia , Linfoma/virologia , Masculino , Pessoa de Meia-Idade , Prevalência , Classe Social
2.
Afr Health Sci ; 21(1): 54-59, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34394281

RESUMO

Background: There has been a growing public health burden of childhood tumours in low and middle income countries (LMICs) as the trend in epidemiological transition continues to vary. Objective: The objective of this report is to determine the spectrum of childhood tumours at a tertiary hospital in Nigeria. Methods: A retrospective review of the histopathology register over the period January 2006 to December 2015. Results: The total paediatric tumour cases was 248, including 143 (57.7%) females and 105 (42.3%) males, aged 0 - 12 years (mean 6.1 years ± 3.97 SD). The age group 2 - 5 year cohort had the highest prevalence of tumour. The predominant tumour based on tissue of origin was epithelial neoplasms 88 (35.5%), vascular neoplasms 56 (22.6%), neural neoplasm 42 (16.9%), mesenchymal neoplasm 37 (14.9%), germ cell neoplasm 13 (5.2%) and haematopoietic neoplasms 12 (4.8%). Majority of the tumours were benign, 148 (59.7%) and malignant 100 (40.3%). The most predominant benign tumour was haemangioma 33 (13.3%) and predominant malignant tumour was lymphoma 22 (8.9%). Conclusion: Benign tumours remain the commonest neoplasm of children in this hospital-based data. Development and implementation of a tumour registry would provide a more comprehensive information.


Assuntos
Hemangioma/patologia , Linfoma/patologia , Neoplasias/patologia , Distribuição por Idade , Criança , Pré-Escolar , Feminino , Hemangioma/epidemiologia , Humanos , Lactente , Recém-Nascido , Linfoma/epidemiologia , Masculino , Neoplasias/epidemiologia , Nigéria/epidemiologia , Prevalência , Sistema de Registros , Estudos Retrospectivos , Distribuição por Sexo , Centros de Atenção Terciária
3.
Int J Mol Sci ; 22(15)2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34361035

RESUMO

B lymphocytes are an indispensable part of the human immune system. They are the effective mediators of adaptive immunity and memory. To accomplish specificity against an antigen, and to establish the related immunologic memory, B cells differentiate through a complicated and strenuous training program that is characterized by multiple drastic genomic modifications. In order to avoid malignant transformation, these events are tightly regulated by multiple checkpoints, the vast majority of them involving bioenergetic alterations. Despite this stringent control program, B cell malignancies are amongst the top ten most common worldwide. In an effort to better understand malignant pathobiology, in this review, we summarize the metabolic swifts that govern normal B cell lymphopoiesis. We also review the existent knowledge regarding malignant metabolism as a means to unravel new research goals and/or therapeutic targets.


Assuntos
Linfócitos B/metabolismo , Linfoma/metabolismo , Linfopoese , Animais , Linfócitos B/citologia , Humanos , Linfoma/patologia , Efeito Warburg em Oncologia
4.
Acta Cytol ; 65(4): 354-357, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34350848

RESUMO

Morphological analysis of the bone marrow is an essential step in the diagnosis of hematological disease. The conventional analysis of bone marrow smears is performed under a manual microscope, which is labor-intensive and subject to interobserver variability. The morphological differential diagnosis of abnormal lymphocytes from normal lymphocytes is still challenging. The digital pathology methods integrated with advances in machine learning enable new diagnostic features/algorithms from digital bone marrow cell images in order to optimize classification, thus providing a robust and faster screening diagnostic tool. We have developed a machine learning system, Morphogo, based on algorithms to discriminate abnormal lymphocytes from normal lymphocytes using digital imaging analysis. We retrospectively reviewed 347 cases of bone marrow digital images. Among them, 53 cases had a clinical history and the diagnosis of marrow involvement with lymphoma was confirmed either by morphology or flow cytometry. We split the 53 cases into two groups for training and testing with 43 and 10 cases, respectively. The selected 15,353 cell images were reviewed by pathologists, based on morphological visual appearance, from 43 patients whose diagnosis was confirmed by complementary tests. To expand the range and the precision of recognizing the lymphoid cells in the marrow by automated digital microscopy systems, we developed an algorithm that incorporated color and texture in addition to geometrical cytological features of the variable lymphocyte images which were applied as the training data set. The selected images from the 10 patients were analyzed by the trained artificial intelligence-based recognition system and compared with the final diagnosis rendered by pathologists. The positive predictive value for the identification of the categories of reactive/normal lymphocytes and abnormal lymphoid cells was 99.04%. It seems likely that further training and improvement of the algorithms will facilitate further subclassification of specific lineage subset pathology, e.g., diffuse large B-cell lymphoma from chronic lymphocytic leukemia/small lymphocytic lymphoma, follicular lymphoma, mantle cell lymphoma or even hairy cell leukemia in cases of abnormal malignant lymphocyte classes in the future. This research demonstrated the feasibility of digital pathology and emerging machine learning approaches to automatically diagnose lymphoma cells in the bone marrow based on cytological-histological analyses.


Assuntos
Células da Medula Óssea/patologia , Exame de Medula Óssea , Diagnóstico por Computador , Interpretação de Imagem Assistida por Computador , Linfócitos/patologia , Linfoma/patologia , Aprendizado de Máquina , Microscopia , Humanos , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos Retrospectivos
5.
Br J Radiol ; 94(1127): 20210448, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34379496

RESUMO

Total metabolic tumor volume (TMTV), a new parameter extracted from baseline FDG-PET/CT, has been recently proposed by several groups as a prognosticator in lymphomas before first-line treatment. TMTV, the sum of the metabolic volume of each lesion, is an index of the metabolically most active part of the tumor and highly correlates with the total tumor burden. TMTV measurement is obtained from PET images processed with different software and techniques, many being now freely available. In the various lymphoma subtypes where it has been measured, such as diffuse large B-cell lymphoma, Hodgkin lymphoma, Follicular Lymphoma, and Peripheral T-cell lymphoma, TMTV has been reported as a strong predictor of outcome (progression-free survival and overall survival) often outperforming the clinical scores, molecular predictors, and results of interim PET. Combined with these scores, TMTV improves the stratification of the populations into risk groups with different outcomes. TMTV cut-off separating the high-risk from the low-risk population impacts the outcome whatever the technique used for its measurement and an international harmonization is ongoing. TMTV is a unique and easy tool that could replace the surrogate of tumor burden included in the prognostic indexes used in lymphoma and help tailor therapy. Other parameters extracted from the baseline PET may give an information on the dissemination of this total tumor volume such as the maximum distance between the lesions. Trials based on TMTV would probably demonstrate its predictive value.


Assuntos
Fluordesoxiglucose F18 , Linfoma/diagnóstico por imagem , Linfoma/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Compostos Radiofarmacêuticos , Carga Tumoral , Humanos , Prognóstico
6.
Am J Clin Pathol ; 156(5): 871-885, 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34406351

RESUMO

OBJECTIVES: Follicular hyperplasias (FHs) with light chain-restricted (LCR) plasmacytoid/plasma cells (PCs) within germinal centers (GCs) based on immunohistochemistry (IHC)/in situ hybridization (ISH) can potentially lead to diagnostic error. This study aims to better characterize such cases, including their clinical implications. METHODS: LC expression by IHC/ISH was quantitatively assessed in GCs of 17 FHs with LCRGCs. BCL2, CD10, BCL6, BCL2, immunoglobulin (Ig) heavy chains, IgG4, and Epstein-Barr encoding region stains were performed. In total, 8 cases had polymerase chain reaction (PCR)-based clonality studies. RESULTS: All cases showed FH, including 4 with progressively transformed GCs (PTGCs); 0.8% to 52% (median, 21%) of the GCs were LCR; 13 of 17 had both κ- and λ-LCRGCs, and 4 of 17 had only κ-LCRGCs; 7 of 16 had prominent intrafollicular IgG4-positive cells. One case demonstrated BCL2-positive cells in focal LCRGCs but lacked BCL2 rearrangement. B-cell monoclonality was demonstrated in 3 of 8 cases (only after microdissection). Seven patients had autoimmune disorders, and 1 had had a transplant. Three patients had a history of lymphoma, 1 developed lymphoma, and 1 developed lymphomatoid granulomatosis subsequently. CONCLUSIONS: FHs with LCRGC by IHC/ISH are typically not associated with the development of lymphoma, even though they can express BCL2 and show monoclonality by PCR. They may be associated with increased intrafollicular IgG4-positive cells, PTGC, and autoimmunity.


Assuntos
Centro Germinativo/imunologia , Centro Germinativo/patologia , Cadeias Leves de Imunoglobulina/imunologia , Plasmócitos/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Feminino , Humanos , Hiperplasia/imunologia , Hiperplasia/patologia , Linfoma/diagnóstico , Linfoma/imunologia , Linfoma/patologia , Transtornos Linfoproliferativos/diagnóstico , Transtornos Linfoproliferativos/imunologia , Transtornos Linfoproliferativos/patologia , Masculino , Pessoa de Meia-Idade , Plasmócitos/patologia , Estudos Retrospectivos
7.
Br J Radiol ; 94(1127): 20210470, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34415777

RESUMO

18F-fluoro-deoxyglucose positron emission tomography (PET)/computed tomography (CT) scans play an important role in the management of lymphoma patients. They are critical to accurately stage disease and assess its response to therapy. In addition, PET/CT scans enable precise target delineation for radiation therapy planning. In this review, we describe the use of PET/CT scans in lymphoma, with a focus on their role in staging disease, assessing response to therapy, predicting prognosis, and planning RT.


Assuntos
Fluordesoxiglucose F18 , Linfoma/diagnóstico por imagem , Linfoma/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Compostos Radiofarmacêuticos , Planejamento da Radioterapia Assistida por Computador/métodos , Humanos , Linfoma/radioterapia , Estadiamento de Neoplasias , Prognóstico
8.
J Med Chem ; 64(14): 10167-10184, 2021 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-34196564

RESUMO

Traditional EZH2 inhibitors are developed to suppress the enzymatic methylation activity, and they may have therapeutic limitations due to the nonenzymatic functions of EZH2 in cancer development. Here, we report proteolysis-target chimera (PROTAC)-based EZH2 degraders to target the whole EZH2 in lymphoma. Two series of EZH2 degraders were designed and synthesized to hijack E3 ligase systems containing either von Hippel-Lindau (VHL) or cereblon (CRBN), and some VHL-based compounds were able to mediate EZH2 degradation. Two best degraders, YM181 and YM281, induced robust cell viability inhibition in diffuse large B-cell lymphoma (DLBCL) and other subtypes of lymphomas, outperforming a clinically used EZH2 inhibitor EPZ6438 (tazemetostat) that was only effective against DLBCL. The EZH2 degraders displayed promising antitumor activities in lymphoma xenografts and patient-derived primary lymphoma cells. Our study demonstrates that EZH2 degraders have better therapeutic activity than EZH2 inhibitors, which may provide a potential anticancer strategy to treat lymphoma.


Assuntos
Antineoplásicos/farmacologia , Desenho de Fármacos , Proteína Potenciadora do Homólogo 2 de Zeste/antagonistas & inibidores , Linfoma/tratamento farmacológico , Proteína Supressora de Tumor Von Hippel-Lindau/antagonistas & inibidores , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Humanos , Linfoma/metabolismo , Linfoma/patologia , Simulação de Acoplamento Molecular , Estrutura Molecular , Relação Estrutura-Atividade , Células Tumorais Cultivadas , Proteína Supressora de Tumor Von Hippel-Lindau/metabolismo
9.
Front Immunol ; 12: 683623, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34220834

RESUMO

Background: B-cell non-Hodgkin's lymphoma (B-NHL) is one of the major complications of primary Sjögren's syndrome (SS). Chronic inflammation and macrophages in SS minor salivary glands have been previously suggested as significant predictors for lymphoma development among SS patients. Lipoprotein-associated phospholipase A2 (Lp-PLA2)-a product mainly of tissue macrophages-is found in the circulation associated with lipoproteins and has been previously involved in cardiovascular, autoimmune, and malignant diseases, including lymphoma. Objective: The purpose of the current study was to investigate the contributory role of Lp-PLA2 in B-NHL development in the setting of primary SS. Methods: Lp-PLA2 activity in serum samples collected from 50 primary SS patients with no lymphoma (SS-nL), 9 primary SS patients with lymphoma (SS-L), and 42 healthy controls (HC) was determined by detection of [3H]PAF degradation products by liquid scintillation counter. Moreover, additional sera from 50 SS-nL, 28 SS-L, and 32 HC were tested for Lp-PLA2 activity using a commercially available ELISA kit. Lp-PLA2 mRNA, and protein expression in minor salivary gland (MSG) tissue samples derived from SS-nL, SS-L patients, and sicca controls (SC) were analyzed by real-time PCR, Western blot, and immunohistochemistry. Results: Serum Lp-PLA2 activity was significantly increased in SS-L compared to both SS-nL and HC by two independent methods implemented [mean ± SD (nmol/min/ml): 62.0 ± 13.4 vs 47.6 ± 14.4 vs 50.7 ± 16.6, p-values: 0.003 and 0.04, respectively, and 19.4 ± 4.5 vs 15.2 ± 3.3 vs 14.5 ± 3.0, p-values: <0.0001, in both comparisons]. ROC analysis revealed that the serum Lp-PLA2 activity measured either by radioimmunoassay or ELISA has the potential to distinguish between SS-L and SS-nL patients (area under the curve [AUC]: 0.8022, CI [95%]: 0.64-0.96, p-value: 0.004 for radioimmunoassay, and AUC: 0.7696, CI [95%]: 0.66-0.88, p-value: <0.0001, for ELISA). Lp-PLA2 expression in MSG tissues was also increased in SS-L compared to SS-nL and SC at both mRNA and protein level. ROC analysis revealed that both MSG mRNA and protein Lp-PLA2 have the potential to distinguish between SS-nL and SS-L patients (area under the curve [AUC] values of 0.8490, CI [95%]: 0.71-0.99, p-value: 0.0019 and 0.9444, CI [95%]: 0.79-1.00, p- value: 0.0389 respectively). No significant difference in either serum Lp-PLA2 activity or MSG tissue expression was observed between SS-nL and HC. Conclusions: Lp-PLA2 serum activity and MSG tissue mRNA/protein expression could be a new biomarker and possibly a novel therapeutic target for B-cell lymphoproliferation in the setting of SS.


Assuntos
1-Alquil-2-acetilglicerofosfocolina Esterase/metabolismo , Linfoma/etiologia , Linfoma/patologia , Síndrome de Sjogren/metabolismo , 1-Alquil-2-acetilglicerofosfocolina Esterase/genética , Adolescente , Adulto , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Linfoma/sangue , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/análise , Radioimunoensaio , Reação em Cadeia da Polimerase em Tempo Real , Síndrome de Sjogren/etiologia , Adulto Jovem
10.
Molecules ; 26(13)2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34202812

RESUMO

The endocannabinoid system (ECS) is a composite cell-signaling system that allows endogenous cannabinoid ligands to control cell functions through the interaction with cannabinoid receptors. Modifications of the ECS might contribute to the pathogenesis of different diseases, including cancers. However, the use of these compounds as antitumor agents remains debatable. Pre-clinical experimental studies have shown that cannabinoids (CBs) might be effective for the treatment of hematological malignancies, such as leukemia and lymphoma. Specifically, CBs may activate programmed cell death mechanisms, thus blocking cancer cell growth, and may modulate both autophagy and angiogenesis. Therefore, CBs may have significant anti-tumor effects in hematologic diseases and may synergistically act with chemotherapeutic agents, possibly also reducing chemoresistance. Moreover, targeting ECS might be considered as a novel approach for the management of graft versus host disease, thus reducing some symptoms such as anorexia, cachexia, fatigue, anxiety, depression, and neuropathic pain. The aim of the present review is to collect the state of the art of CBs effects on hematological tumors, thus focusing on the essential topics that might be useful before moving into the clinical practice.


Assuntos
Canabinoides/uso terapêutico , Neoplasias Hematológicas , Proteínas de Neoplasias/metabolismo , Receptores de Canabinoides/metabolismo , Neoplasias Hematológicas/tratamento farmacológico , Neoplasias Hematológicas/metabolismo , Neoplasias Hematológicas/patologia , Humanos , Leucemia/tratamento farmacológico , Leucemia/metabolismo , Leucemia/patologia , Linfoma/tratamento farmacológico , Linfoma/metabolismo , Linfoma/patologia
11.
BMC Cancer ; 21(1): 754, 2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34187419

RESUMO

BACKGROUND: Corticosteroid therapy (CST) prior to biopsy may hinder histopathological diagnosis in primary central nervous system lymphoma (PCNSL). Therefore, preoperative CST in patients with suspected PCNSL should be avoided if clinically possible. The aim of this study was thus to analyze the difference in the rate of diagnostic surgeries in PCNSL patients with and without preoperative CST. METHODS: A multicenter retrospective study including all immunocompetent patients diagnosed with PCNSL between 1/2004 and 9/2018 at four neurosurgical centers in Austria was conducted and the results were compared to literature. RESULTS: A total of 143 patients were included in this study. All patients showed visible contrast enhancement on preoperative MRI. There was no statistically significant difference in the rate of diagnostic surgeries with and without preoperative CST with 97.1% (68/70) and 97.3% (71/73), respectively (p = 1.0). Tapering and pause of CST did not influence the diagnostic rate. Including our study, there are 788 PCNSL patients described in literature with an odds ratio for inconclusive surgeries after CST of 3.3 (CI 1.7-6.4). CONCLUSIONS: Preoperative CST should be avoided as it seems to diminish the diagnostic rate of biopsy in PCNSL patients. Yet, if CST has been administered preoperatively and there is still a contrast enhancing lesion to target for biopsy, surgeons should try to keep the diagnostic delay to a minimum as the likelihood for acquiring diagnostic tissue seems sufficiently high.


Assuntos
Corticosteroides/uso terapêutico , Corticosteroides/farmacologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Sistema Nervoso Central/patologia , Feminino , Humanos , Linfoma/patologia , Masculino , Pessoa de Meia-Idade , Período Pré-Operatório , Estudos Retrospectivos , Adulto Jovem
12.
PLoS Pathog ; 17(6): e1009618, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34106998

RESUMO

Subpopulations of B-lymphocytes traffic to different sites and organs to provide diverse and tissue-specific functions. Here, we provide evidence that epigenetic differences confer a neuroinvasive phenotype. An EBV+ B cell lymphoma cell line (M14) with low frequency trafficking to the CNS was neuroadapted to generate a highly neuroinvasive B-cell population (MUN14). MUN14 B cells efficiently infiltrated the CNS within one week and produced neurological pathologies. We compared the gene expression profiles of viral and cellular genes using RNA-Seq and identified one viral (EBNA1) and several cellular gene candidates, including secreted phosphoprotein 1/osteopontin (SPP1/OPN), neuron navigator 3 (NAV3), CXCR4, and germinal center-associated signaling and motility protein (GCSAM) that were selectively upregulated in MUN14. ATAC-Seq and ChIP-qPCR revealed that these gene expression changes correlated with epigenetic changes at gene regulatory elements. The neuroinvasive phenotype could be attenuated with a neutralizing antibody to OPN, confirming the functional role of this protein in trafficking EBV+ B cells to the CNS. These studies indicate that B-cell trafficking to the CNS can be acquired by epigenetic adaptations and provide a new model to study B-cell neuroinvasion associated CNS lymphoma and autoimmune disease of the CNS, including multiple sclerosis (MS).


Assuntos
Linfócitos B/patologia , Linfócitos B/virologia , Neoplasias do Sistema Nervoso Central/virologia , Epigênese Genética , Infecções por Vírus Epstein-Barr/patologia , Animais , Linfócitos B/metabolismo , Transformação Celular Viral/fisiologia , Neoplasias do Sistema Nervoso Central/metabolismo , Neoplasias do Sistema Nervoso Central/patologia , Infecções por Vírus Epstein-Barr/genética , Infecções por Vírus Epstein-Barr/metabolismo , Herpesvirus Humano 4 , Linfoma/metabolismo , Linfoma/patologia , Linfoma/virologia , Camundongos , Osteopontina/metabolismo
13.
Radiologe ; 61(7): 611-618, 2021 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-34160645

RESUMO

CLINICAL/METHODOLOGICAL ISSUE: Lymphoma is the third most common neoplasm in children. Detection, accurate staging, and restaging are important for all radiologists involved in the diagnosis of children. STANDARD RADIOLOGICAL METHODS: Magnetic resonance imaging (MRI), positron emission tomography/computed tomography (PET/CT), CT, ultrasound, X­ray. METHODOLOGICAL INNOVATIONS: Whole-body imaging (MRI and PET-MRI or PET-CT) play a key role in diagnostics and for therapy selection in Hodgkin lymphoma. PERFORMANCE: In particular, hybrid imaging using 18F­FDG PET is proving to be a powerful method for staging and restaging. ACHIEVEMENTS: Standardization of imaging and inclusion in therapy studies (e.g. within the framework of the EuroNet-PHL-C2 study) improves diagnostics and simultaneously reduces therapy-related side effects. PRACTICAL RECOMMENDATIONS: In Hodgkin lymphoma, deviations from the prescribed diagnostic procedure should be avoided. In clinically very heterogeneous non-Hodgkin lymphoma (NHL), on the other hand, the diagnostic procedure should be adapted to the actual clinical condition of the child. The role of interim PET in NHL is currently still the subject of clinical discussion.


Assuntos
Linfoma , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Adolescente , Criança , Fluordesoxiglucose F18 , Humanos , Linfoma/diagnóstico por imagem , Linfoma/patologia , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Imagem Corporal Total
14.
Front Immunol ; 12: 669881, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34054841

RESUMO

Proper lymphopoiesis and immune responses depend on the spatiotemporal control of multiple processes, including gene expression, DNA recombination and cell fate decisions. High-order 3D chromatin organization is increasingly appreciated as an important regulator of these processes and dysregulation of genomic architecture has been linked to various immune disorders, including lymphoid malignancies. In this review, we present the general principles of the 3D chromatin topology and its dynamic reorganization during various steps of B and T lymphocyte development and activation. We also discuss functional interconnections between architectural, epigenetic and transcriptional changes and introduce major key players of genomic organization in B/T lymphocytes. Finally, we present how alterations in architectural factors and/or 3D genome organization are linked to dysregulation of the lymphopoietic transcriptional program and ultimately to hematological malignancies.


Assuntos
Linfócitos B/imunologia , Transformação Celular Neoplásica/imunologia , Montagem e Desmontagem da Cromatina , Leucemia/imunologia , Ativação Linfocitária , Linfoma/imunologia , Linfopoese , Linfócitos T/imunologia , Animais , Linfócitos B/metabolismo , Linfócitos B/patologia , Diferenciação Celular , Linhagem da Célula , Proliferação de Células , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Transformação Celular Neoplásica/patologia , Epigênese Genética , Regulação Leucêmica da Expressão Gênica , Humanos , Leucemia/genética , Leucemia/metabolismo , Leucemia/patologia , Linfoma/genética , Linfoma/metabolismo , Linfoma/patologia , Fenótipo , Linfócitos T/metabolismo , Linfócitos T/patologia
15.
J Oleo Sci ; 70(5): 665-673, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33952791

RESUMO

Cancer is the world's biggest health problem and cancer-induced mortality happened all over the planet after the heart disease. The present study was to scrutinize the anti-leukemia effect of diosmin against Dalton Ascitic Lymphoma (DAL) induced leukemia in mice. DAL cell was used for induction the solid tumor. Body weight, life spans, tumor volume and mean survival time was estimated. Antioxidant, biochemical and pro-inflammatory cytokines were estimated. Diosmin showed the cell viability effect at dose dependent manner against the both cell lines. DAL induced solid tumor mice showed the decreased body weight, mean survival days, non viable cell count and increased the tumor volume, viable cell count and diosmin significantly (p < 0.001) reverse the effect of DAL. Diosmin significantly (p < 0.001) altered the hematological, differential leukocytes, antioxidant, biochemical, pro-inflammatory cytokines at dose dependently. Collectively, we can say that diosmin might alter the DAL induced abnormality via antioxidant and anti-inflammatory effects.


Assuntos
Anti-Inflamatórios , Antineoplásicos Fitogênicos , Ascite/patologia , Sobrevivência Celular/efeitos dos fármacos , Diosmina/farmacologia , Leucemia/patologia , Linfoma/patologia , Animais , Antioxidantes , Células Cultivadas , Citrus/química , Citocinas/metabolismo , Diosmina/administração & dosagem , Diosmina/isolamento & purificação , Relação Dose-Resposta a Droga , Mediadores da Inflamação/metabolismo , Leucemia/tratamento farmacológico , Leucemia/metabolismo , Linfoma/tratamento farmacológico , Linfoma/metabolismo , Camundongos Endogâmicos BALB C , Fitoterapia
16.
Am J Hematol ; 96(8): 979-988, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-33971040

RESUMO

The development of cardiovascular disease (CVD) in long-term survivors of lymphoma is of increasing importance. Here, we characterize the cumulative incidence and risk factors for CVD in lymphoma patients diagnosed in the current treatment era. From 2002-2015, newly diagnosed lymphoma patients (>18 years) were enrollment into a prospective cohort study that captured incident CVD, consisting of congestive heart failure (CHF), acute coronary syndrome (ACS), valvular heart disease (VHD), and arrhythmia. The cumulative incidence of CVD was calculated with death modeled as a competing risk. We estimated the association of treatment with anthracyclines or radiotherapy and traditional CVD risk factors with incidence of CVD using hazard ratios (HR) and 95% confidence intervals (CI) estimated from Cox regression. After excluding prevalent CVD at lymphoma diagnosis, the study consisted of 3063 patients with a median age of 59 years (range 18-95). The cumulative incidence of CVD at 10-years was 10.7% (95% CI, 9.5%-12.1%). In multivariable analysis, increasing age (HR = 1.05 per year, p < 0.001), male sex (HR = 1.36, p = 0.02), current smoker (HR = 2.10, p < 0.001), BMI > 30 kg/m2 (HR = 1.45, p = 0.01), and any anthracycline treatment (HR = 1.57, p < 0.001) were all significantly associated with risk of CVD. Anthracyclines were associated with increased risk of CHF (HR = 2.71, p < 0.001) and arrhythmia (HR = 1.61, p < 0.01), but not VHD (HR = 0.84, p = 0.58) or ACS (HR = 1.32, p = 0.24) after adjustment for CVD risk factors. Even in the modern treatment era, CVD remains common in lymphoma survivors and preventive efforts are required that address both treatment and CVD risk factors.


Assuntos
Antraciclinas/uso terapêutico , Doenças Cardiovasculares/fisiopatologia , Linfoma/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antraciclinas/farmacologia , Estudos de Coortes , Feminino , Humanos , Linfoma/patologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Adulto Jovem
17.
World Neurosurg ; 151: e979-e987, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34020062

RESUMO

OBJECTIVE: Preoperative differentiation of lymphoma from other aggressive intracranial neoplasms is important as the surgical and adjuvant therapy may be fundamentally different between the 2 types of tumors. The purpose of this study was to assess the ability of the dynamic susceptibility contrast-derived metrics, percentage signal recovery (PSR) ratio, and relative cerebral blood volume (rCBV) to distinguish between primary central nervous system lymphoma (PCNSL) and high-grade glioma (HGG). METHODS: Twenty-six patients (15 with HGG and 11 with PCNSL) with histologically confirmed diagnoses were retrospectively analyzed. Mean PSR and rCBV were calculated from dynamic susceptibility contrast imaging. The 2 groups were compared using an independent samples t-test. Receiver operating characteristic analyses were performed to determine the area under the curve and identify threshold values to differentiate PCNSL from GBM. RESULTS: Both rCBV and PSR values were significantly different, at both the group level and subject level, between the PCNSL and HGG patients. The mean rCBV was significantly lower in PCNSL (1.38 ± 0.64) compared with HGG (5.19 ± 2.21, df = 11.24, P < 0.001). The mean PSR ratio was significantly higher in PCNSL (1.04 ± 0.11) compared with HGG (0.72 ± 0.16, df = 17.23, P < 0.001). An rCBV threshold value of 2.67 provided a 100% sensitivity and 100% specificity (area under the curve 1.0) for differentiating PCNSL from HGG. A PSR ratio threshold value of 0.9 was 100% sensitive and 90.91% specific for differentiating PCNSL from HGG. CONCLUSIONS: The findings of our study show that rCBV and PSR ratio are different in HGG and PCNSL at both the group level and subject level. Incorporation of perfusion in routine magnetic resonance imaging of contrast-enhancing lesions can have a significant impact on patient management.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Glioma/diagnóstico por imagem , Interpretação de Imagem Assistida por Computador/métodos , Linfoma/diagnóstico por imagem , Neuroimagem/métodos , Neoplasias Encefálicas/patologia , Diagnóstico Diferencial , Imagem de Difusão por Ressonância Magnética/métodos , Glioma/patologia , Humanos , Linfoma/patologia , Projetos Piloto , Estudos Retrospectivos
18.
Am J Surg Pathol ; 45(8): 1138-1150, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34010155

RESUMO

Early recognition of adult-onset immunodeficiency associated with neutralizing anti-interferon gamma autoantibodies (anti-IFNγ Abs) remains difficult, and misdiagnoses have been reported. Although febrile lymphadenopathy is among the most common initial manifestations of this disorder, no comprehensive clinicopathologic analysis of lymphadenopathy in patients with anti-IFNγ Abs has been reported. Here, we describe 26 lymph node biopsy specimens from 16 patients. All patients exhibited concurrent disseminated nontuberculous mycobacterial infections, and 31% received a tentative diagnosis of lymphoma at initial presentation. We found 3 distinct histomorphologic patterns: well-formed granuloma (46%), suppurative inflammation or loose histiocytic aggregates (31%), and lymphoproliferative disorder (LPD, 23%). The latter shared some of the features of malignant T-cell lymphoma, IgG4-related disease, and multicentric Castleman disease. Half of the specimens with LPD had monoclonal T cells, and 33.3% were indistinguishable from angioimmunoblastic T-cell lymphoma as per current diagnostic criteria. All lymphadenopathy with LPD features regressed with antibiotics without administration of cytotoxic chemotherapy or immunotherapy. The median follow-up time was 4.3 years. Our study highlights the substantial challenge of distinguishing between lymphoma and other benign lymphadenopathy in the setting of neutralizing anti-IFNγ Abs. Increased vigilance and multidisciplinary discussion among clinicians and pathologists are required to achieve the most appropriate diagnosis and management.


Assuntos
Síndromes de Imunodeficiência/diagnóstico , Linfadenopatia/diagnóstico , Linfoma/diagnóstico , Linfócitos T/imunologia , Adulto , Idoso , Antibacterianos , Anticorpos Neutralizantes , Autoanticorpos/imunologia , Autoantígenos/imunologia , Proliferação de Células , Feminino , Humanos , Síndromes de Imunodeficiência/imunologia , Síndromes de Imunodeficiência/patologia , Interferon gama/imunologia , Linfonodos/patologia , Linfadenopatia/imunologia , Linfadenopatia/patologia , Linfoma/imunologia , Linfoma/patologia , Masculino , Pessoa de Meia-Idade , Infecções Oportunistas/imunologia , Infecções Oportunistas/patologia
19.
Pediatr Surg Int ; 37(8): 1049-1059, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33963920

RESUMO

PURPOSE: Complete upfront resection of pediatric gastrointestinal lymphomas is recommended over biopsy whenever feasible, but either approach may have adverse sequelae. We sought to compare gastrointestinal and oncological outcomes of pediatric gastrointestinal lymphomas who underwent attempted upfront resection or biopsy of the presenting bowel mass. METHODS: We retrospectively reviewed charts of children with gastrointestinal lymphomas treated on LMB89 and LMB96 protocols from 2000 to 2019 who underwent upfront gastrointestinal surgery, and compared resection and biopsy groups. RESULTS: Of 33 children with abdominal lymphomas, 20 had upfront gastrointestinal surgery-10 each had resection or biopsy. Patients with attempted upfront resections had fewer postoperative gastrointestinal complications compared to biopsies (10% vs. 60%, p = 0.057), but longer time to chemotherapy initiation (median 11.5 vs. 4.5 days, p < 0.001). Three resection patients were surgically down-staged. Second surgeries were required in 30% and 40% of resected and biopsied patients, respectively, at median 4.6 months. Survival was similar in both groups, but better in patients on LMB96 protocol and stage II/III disease. CONCLUSIONS: Children with upfront attempted resection had low rates of surgical down-staging, greater delay in chemotherapy initiation, but fewer gastrointestinal complications and subsequent surgeries than biopsies. Survival was similar regardless of upfront surgery, likely reflecting beneficial effects of newer protocols.


Assuntos
Biópsia , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Neoplasias do Íleo/cirurgia , Linfoma/cirurgia , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Criança , Pré-Escolar , Ciclofosfamida/uso terapêutico , Citarabina/uso terapêutico , Feminino , Humanos , Neoplasias do Íleo/tratamento farmacológico , Neoplasias do Íleo/patologia , Lactente , Linfoma/tratamento farmacológico , Linfoma/patologia , Masculino , Metotrexato/uso terapêutico , Estudos Retrospectivos
20.
Lancet Haematol ; 8(6): e433-e445, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34048682

RESUMO

BACKGROUND: Novel approaches are required to improve outcomes in relapsed or refractory classical Hodgkin lymphoma and non-Hodgkin lymphoma. We aimed to evaluate camidanlumab tesirine, an anti-CD25 antibody-drug conjugate, in this patient population. METHODS: This was a phase 1, dose-escalation (part 1), dose-expansion (part 2), multicentre trial done in 12 hospital sites (seven in the USA and five in the UK). Adults (≥18 years old) with pathologically confirmed relapsed or refractory classical Hodgkin lymphoma or non-Hodgkin lymphoma, an Eastern Cooperative Oncology Group performance status 0-2, who had no therapies available to them with established clinical benefit for their disease stage were enrolled. Camidanlumab tesirine was administered intravenously (3-150 µg/kg) once every 3 weeks. Primary objectives were to assess dose-limiting toxicity, determine maximum tolerated dose and recommended expansion dose(s), and assess safety of camidanlumab tesirine. Safety was assessed in all treated patients; antitumour activity was assessed in patients with one or more valid baseline and post-baseline disease assessment and in those who had disease progression or died after first study-drug dose. This trial was registered with ClinicalTrials.gov, NCT02432235. FINDINGS: Between Oct 5, 2015, and Jun 30, 2019, 133 patients were enrolled (77 [58%] had classical Hodgkin lymphoma and 56 (42%) had non-Hodgkin lymphoma). Median follow-up was 9·2 months (IQR 4·2-14·3). Eight dose-limiting toxicities were reported in five (6%) of 86 patients who were evaluable; the maximum tolerated dose was not reached. The recommended doses for expansion were 30 µg/kg and 45 µg/kg for patients with classical Hodgkin lymphoma and 80 µg/kg for patients with T-cell non-Hodgkin lymphomas. No recommended doses for expansion were defined for B-cell non-Hodgkin lymphomas. Grade 3 or worse treatment-emergent adverse events (reported by ≥10% of the 133 patients) included increased γ-glutamyltransferase (20 [15%] patients), maculopapular rash (16 [12%]), and anaemia (15 [11%]); 74 (56%) patients had serious treatment-emergent adverse events, most commonly pyrexia (16 [12%]). One (1%) fatal treatment-emergent adverse event and two (2%) deaths outside the reporting period were considered at least possibly study-drug related. Antitumoural activity was seen in classical Hodgkin and non-Hodgkin lymphomas; notably in all patients with classical Hodgkin lymphoma, the overall response was 71% (95% CI 60-81). INTERPRETATION: These results warrant evaluation of camidanlumab tesirine as a potential treatment option for relapsed or refractory lymphoma, particularly in patients with classical Hodgkin lymphoma. FUNDING: ADC Therapeutics.


Assuntos
Imunoconjugados/uso terapêutico , Linfoma/tratamento farmacológico , Administração Intravenosa , Adulto , Idoso , Esquema de Medicação , Exantema/etiologia , Exantema/patologia , Feminino , Febre/etiologia , Febre/patologia , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/patologia , Humanos , Imunoconjugados/efeitos adversos , Subunidade alfa de Receptor de Interleucina-2/imunologia , Estimativa de Kaplan-Meier , Linfoma/mortalidade , Linfoma/patologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva , Índice de Gravidade de Doença , Resultado do Tratamento
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