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1.
Autops. Case Rep ; 9(4): e2019117, Oct.-Dec. 2019. ilus
Artigo em Inglês | LILACS | ID: biblio-1024240

RESUMO

Sporadic Burkitt lymphoma (SBL) is a variant of Burkitt lymphoma that occurs worldwide, affecting mainly children and young adults. Association with Epstein-Barr virus (EBV) can be identified in approximately 20-30% of cases. Herein we described a case of a 63-year-old male presenting intraoral bilateral mandibular swelling, subjacent to fixed dental prosthesis, with one month of duration. Incisional biopsies were performed, and after two days, the patient was hospitalized due to malaise and breathing difficulty, and died after a week when an abdominal tumor was detected. The mandibular biopsies revealed a diffuse proliferation of medium-sized monomorphic atypical lymphoid cells exhibiting numerous mitoses and areas of "starry-sky" pattern. The tumor showed immunohistochemical positivity for CD20, CD10, Bcl-6, and Ki-67 (≈ 100%); it was negative for CD3, Bcl-2, Vs38c, and MUM-1. Positivity for EBV was found by in situ hybridization. The final diagnosis was intraoral SBL positive for EBV. Clinical, morphological and molecular criteria are necessary for the correct diagnosis of aggressive B-cell neoplasms positive for EBV in elderly patients.


Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/patologia , Linfoma de Burkitt/patologia , Herpesvirus Humano 4 , Linfoma não Hodgkin/patologia
2.
Anticancer Res ; 39(11): 6413-6416, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704875

RESUMO

BACKGROUND/AIM: The aim of this study was to present the clinical characteristics, natural history and survival outcomes of primary gastrointestinal non-Hodgkin lymphomas (PGINHL) in the pediatric population. PATIENTS AND METHODS: Surveillance, Epidemiology, and End Results (SEER) database was queried for patients aged 0 to 19 years with PGINHL between 1973 and 2014. RESULTS: A total of 452 cases were identified [mean age 11.0 (±5.1)] years, whites 84.1%, males (76.5%). The majority of tumors were noted in the small bowel (SB) (47.6%), followed by large bowel (LB) (28.5%) and the stomach (10.0%). Overall, the most common histological subtype was Burkitt lymphoma (51.8%), followed by diffuse large B-cell lymphoma (DLBCL) (26.1%). Mean overall survival (OS) of the entire cohort was 33,33 years with a 5-yr, 10-yr and 30-yr survival rate of 86%, 86% and 79%, respectively. Large bowel tumors had the best long-term survival rates whereas; gastric tumors had the worst with 30-yr survival rate 84% and 74%, respectively. Overall, 328 (72.6%) patients received surgery. No significant survival difference was noted between patients who underwent surgery and those who did not. CONCLUSION: This study presents the largest dataset of pediatric PGINHL and describes the clinical features and outcomes of these patients in addition to summarizing the literature.


Assuntos
Neoplasias Gastrointestinais , Linfoma não Hodgkin , Adolescente , Linfoma de Burkitt/mortalidade , Linfoma de Burkitt/patologia , Linfoma de Burkitt/cirurgia , Neoplasias do Ceco/mortalidade , Neoplasias do Ceco/patologia , Neoplasias do Ceco/cirurgia , Criança , Pré-Escolar , Feminino , Neoplasias Gastrointestinais/mortalidade , Neoplasias Gastrointestinais/patologia , Neoplasias Gastrointestinais/cirurgia , Humanos , Neoplasias do Íleo/mortalidade , Neoplasias do Íleo/patologia , Neoplasias do Íleo/cirurgia , Lactente , Recém-Nascido , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/patologia , Linfoma Difuso de Grandes Células B/cirurgia , Linfoma não Hodgkin/mortalidade , Linfoma não Hodgkin/patologia , Linfoma não Hodgkin/cirurgia , Masculino , Programa de SEER , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Taxa de Sobrevida , Adulto Jovem
3.
Magy Seb ; 72(3): 112-114, 2019 Sep.
Artigo em Húngaro | MEDLINE | ID: mdl-31544481

RESUMO

Introduction: Lymphomas are rare entities in the gastrointestinal tract. The so-called Burkitt-like lymphoma belongs to the non-Hodgkin lymphoma group, and it is quite an aggressive, rapid-growing, but potentially curable disease. Surgeons mostly encounter with this tumor as a solid mass which causes abdominal pain, or as a cause of bowel obstruction or perforation. Our aim was to present a case, when Burkitt-like lymphoma caused acute abdominal symptoms without alarming complaints, obstruction or perforation. Furthermore we review and summarize the relevant literature data on this topic. Regarding our case we can claim that histological investigation and multidisciplinary approach are essential to make the diagnosis and to start the treatment as early as possible.


Assuntos
Abdome Agudo/etiologia , Linfoma de Burkitt/patologia , Dor Abdominal/etiologia , Humanos , Obstrução Intestinal/etiologia
4.
Medicine (Baltimore) ; 98(29): e16222, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31335672

RESUMO

RATIONALE: HIV-related lymphoma, especially non-Hodgkin lymphoma, is one of the most common malignant tumors in HIV/acquired immune deficiency syndrome (AIDS) patients. Autologous hematopoietic stem cell transplantation (AHSCT) for the patients with Burkitt lymphoma (BL) is needed to be further explored. PATIENT CONCERNS: A 57-year-old man was hospitalized with intermittent pain on upper abdomen and melena for >1 month. DIAGNOSIS: HIV antibody testing was positive. The upper gastrointestinal endoscopy was performed and histopathology and immunohistochemistry revealed BL. INTERVENTIONS: Highly effective antiretroviral therapy and sixth cycles of chemotherapy were administered, followed by autologous hematopoietic stem cell transplantation. OUTCOMES: The patient has had tumor-free survival for >6 years with normal CD4+ T cell counts and HIV viral load below the lowest detection LESSONS:: The patient was treated with AHSCT followed complete remission after chemotherapy and achieved long-term disease-free survival. AHSCT may be a promising way for clinical cure of HIV-related BL.


Assuntos
Terapia Antirretroviral de Alta Atividade/métodos , Linfoma de Burkitt , Infecções por HIV , Transplante de Células-Tronco Hematopoéticas/métodos , Condicionamento Pré-Transplante/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Linfoma de Burkitt/complicações , Linfoma de Burkitt/patologia , Linfoma de Burkitt/cirurgia , Intervalo Livre de Doença , Endoscopia Gastrointestinal/métodos , Infecções por HIV/complicações , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Transplante Autólogo/métodos , Resultado do Tratamento , Carga Viral/métodos
5.
Medicine (Baltimore) ; 98(26): e16129, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31261533

RESUMO

Individuals infected with human immunodeficiency virus (HIV) have higher morbidity and mortality due to cancer, which is the third most common cause of death in this group, despite the high effectiveness of antiretroviral therapy (ART). We describe the clinical and laboratory characteristics, initial staging and outcome of HIV-related lymphoma.We included 18 patients in the study, of whom 61.1% were male, mean age 41 years. Nine of the 18 patients (50%) had a diagnosis of HIV infection concurrent with the diagnosis of lymphoma.The most common histological types were diffuse non-Hodgkin B-cell lymphoma, 8 patients (44.4%); and Burkitt lymphoma, 5 (27.8%) cases. The Cotswold revision of the Ann Arbor staging classification in 14 patients (77.7%) was between III and IV. B Symptoms were present in 11 patients (61.1%), bulky mass was observed in 11 cases (61.1%) and had extra-nodal involvement in 8 patients (44.4%).Of the 18 cases analyzed, 8 followed on to second-line treatment, wherein the CODOX-M/IVAC scheme (cyclophosphamide, adriamycin, vincristine, methotrexate/ifosfamide, etoposide, and cytosine arabinoside) was used in 3 of the cases. The second most common scheme was etoposide, doxorubicin, vincristine and cyclophosphamide (EPOCH), used in 2 cases (25%), while in single cases (12.5% each) cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone (CHOEP), ifosfamide, etoposide, and carboplatin (ICE) and dexamethasone, cisplatin, and cytarabine (DHAP) were used.In this series, we observed very high mortality, equivalent to 44.4%, and a complete response in only 11.1%, much lower than that observed by other authors.We found that patients diagnosed with lymphoma associated with HIV had an advanced early clinical staging, and evolved with low response rates to chemotherapy.


Assuntos
Linfoma Relacionado a AIDS/epidemiologia , Linfoma Relacionado a AIDS/terapia , Adulto , Antineoplásicos/uso terapêutico , Linfoma de Burkitt/epidemiologia , Linfoma de Burkitt/patologia , Linfoma de Burkitt/terapia , Feminino , Humanos , Linfoma Relacionado a AIDS/patologia , Linfoma não Hodgkin/epidemiologia , Linfoma não Hodgkin/patologia , Linfoma não Hodgkin/terapia , Masculino , Estadiamento de Neoplasias , Estudos Retrospectivos
7.
PLoS Pathog ; 15(4): e1007541, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-31017975

RESUMO

DNA damage response (DDR) and selective autophagy both can be activated by reactive oxygen/nitrogen species (ROS/RNS), and both are of paramount importance in cancer development. The selective autophagy receptor and ubiquitin (Ub) sensor p62 plays a key role in their crosstalk. ROS production has been well documented in latent infection of oncogenic viruses including Epstein-Barr Virus (EBV). However, p62-mediated selective autophagy and its interplay with DDR have not been investigated in these settings. In this study, we provide evidence that considerable levels of p62-mediated selective autophagy are spontaneously induced, and correlate with ROS-Keap1-NRF2 pathway activity, in virus-transformed cells. Inhibition of autophagy results in p62 accumulation in the nucleus, and promotes ROS-induced DNA damage and cell death, as well as downregulates the DNA repair proteins CHK1 and RAD51. In contrast, MG132-mediated proteasome inhibition, which induces rigorous autophagy, promotes p62 degradation but accumulation of the DNA repair proteins CHK1 and RAD51. However, pretreatment with an autophagy inhibitor offsets the effects of MG132 on CHK1 and RAD51 levels. These findings imply that p62 accumulation in the nucleus in response to autophagy inhibition promotes proteasome-mediated CHK1 and RAD51 protein instability. This claim is further supported by the findings that transient expression of a p62 mutant, which is constitutively localized in the nucleus, in B cell lines with low endogenous p62 levels recaptures the effects of autophagy inhibition on CHK1 and RAD51 protein stability. These results indicate that proteasomal degradation of RAD51 and CHK1 is dependent on p62 accumulation in the nucleus. However, small hairpin RNA (shRNA)-mediated p62 depletion in EBV-transformed lymphoblastic cell lines (LCLs) had no apparent effects on the protein levels of CHK1 and RAD51, likely due to the constitutive localization of p62 in the cytoplasm and incomplete knockdown is insufficient to manifest its nuclear effects on these proteins. Rather, shRNA-mediated p62 depletion in EBV-transformed LCLs results in significant increases of endogenous RNF168-γH2AX damage foci and chromatin ubiquitination, indicative of activation of RNF168-mediated DNA repair mechanisms. Our results have unveiled a pivotal role for p62-mediated selective autophagy that governs DDR in the setting of oncogenic virus latent infection, and provide a novel insight into virus-mediated oncogenesis.


Assuntos
Autofagia , Transformação Celular Viral , Dano ao DNA , Infecções por Vírus Epstein-Barr/patologia , Estresse Oxidativo , Proteínas de Ligação a RNA/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Linfoma de Burkitt/genética , Linfoma de Burkitt/metabolismo , Linfoma de Burkitt/patologia , Linfoma de Burkitt/virologia , Cromatina , Reparo do DNA , Infecções por Vírus Epstein-Barr/genética , Infecções por Vírus Epstein-Barr/metabolismo , Infecções por Vírus Epstein-Barr/virologia , Herpesvirus Humano 4/fisiologia , Humanos , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Complexo de Endopeptidases do Proteassoma , Proteínas de Ligação a RNA/genética , Transdução de Sinais , Ubiquitina/metabolismo , Latência Viral
8.
BMC Cancer ; 19(1): 322, 2019 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-30953469

RESUMO

BACKGROUND: MYC is a heterogeneously expressed transcription factor that plays a multifunctional role in many biological processes such as cell proliferation and differentiation. It is also associated with many types of cancer including the malignant lymphomas. There are two types of aggressive B-cell lymphoma, namely Burkitt lymphoma (BL) and a subgroup of diffuse large cell lymphoma (DLBCL), which both carry MYC translocations and overexpress MYC but both differ significantly in their clinical outcome. In DLBCL, MYC translocations are associated with an aggressive behavior and poor outcome, whereas MYC-positive BL show a superior outcome. METHODS: To shed light on this phenomenon, we investigated the different modes of actions of MYC in aggressive B-cell lymphoma cell lines subdivided into three groups: (i) MYC-positive BL, (ii) DLBCL with MYC translocation (DLBCLpos) and (iii) DLBCL without MYC translocation (DLBCLneg) for control. In order to identify genome-wide MYC-DNA binding sites a chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-Seq) was performed. In addition, ChIP-Seq for H3K4me3 was used for determination of genomic regions accessible for transcriptional activity. These data were supplemented with gene expression data derived from RNA-Seq. RESULTS: Bioinformatics integration of all data sets revealed different MYC-binding patterns and transcriptional profiles in MYC-positive BL and DLBCL cell lines indicating different functional roles of MYC for gene regulation in aggressive B-cell lymphomas. Based on this multi-omics analysis we identified ADGRE5 (alias CD97) - a member of the EGF-TM7 subfamily of adhesion G protein-coupled receptors - as a MYC target gene, which is specifically expressed in BL but not in DLBCL regardless of MYC translocation. CONCLUSION: Our study describes a diverse genome-wide MYC-DNA binding pattern in BL and DLBCL cell lines with and without MYC translocations. Furthermore, we identified ADREG5 as a MYC target gene able to discriminate between BL and DLBCL irrespectively of the presence of MYC breaks in DLBCL. Since ADGRE5 plays an important role in tumor cell formation, metastasis and invasion, it might also be instrumental to better understand the different pathobiology of BL and DLBCL and help to explain discrepant clinical characteristics of BL and DLBCL.


Assuntos
Antígenos CD/genética , Linfoma de Burkitt/genética , Regulação Neoplásica da Expressão Gênica , Linfoma Difuso de Grandes Células B/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Linfoma de Burkitt/patologia , Linhagem Celular Tumoral , Biologia Computacional , Conjuntos de Dados como Assunto , Perfilação da Expressão Gênica , Humanos , Linfoma Difuso de Grandes Células B/patologia , Proteínas Proto-Oncogênicas c-myc/genética , Análise de Sequência de RNA , Translocação Genética
9.
Int J Pediatr Otorhinolaryngol ; 121: 127-136, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30897372

RESUMO

INTRODUCTION: Burkitt lymphoma (BL), an aggressive form of B-cell non-Hodgkin's lymphoma, arising from the nose and paranasal sinuses is relatively rare. It can present with various symptoms leading to potential misdiagnosis and delayed treatment. BL is fatal if left untreated, while early identification and treatment can improve prognosis. OBJECTIVES: 1) To review clinical presentations and sites of involvement of six cases of pediatric BL with rhinologic manifestations and compare these with the current literature. 2) To raise awareness on the variety of presentations of BL in this particular anatomic location. METHODS: A series of six cases of pediatric (0-18 years) BL with rhinologic manifestations is presented. Age, sex, ethnicity, symptoms, imaging, staging, treatment and outcome were recorded. A systematic review of literature was also conducted using PRISMA guidelines. The search strategy used keywords related to rhinologic manifestations of BL (nasal cavity, nasopharynx, paranasal sinus etc.; Burkitt etc.) and included studies published in English and French describing patients 0-18 years of age. RESULTS: 42 patients were included (six from case series and 36 from current literature). Most common presenting symptoms were: nasal obstruction (29%), facial swelling (24%), headache (21%) and proptosis (19%). Most frequent sites of presentation were: nasopharynx (40%), maxilla (40%) and sphenoid (33%). More than half (60%) had systemic involvement, of which the most common locations were: kidney (19%), pancreas (17%) and liver (17%). Mortality from BL in children from this study population was correlated with a longer duration of symptoms prior to presentation, as well as a misdiagnosis preceding the final diagnosis of BL. CONCLUSIONS: This study brings understanding to the numerous presentations of the same aggressive disease, promotes high clinical suspicion when evaluating common otolaryngologic symptoms and can guide healthcare providers in diagnosing pediatric BL with rhinologic manifestations.


Assuntos
Linfoma de Burkitt/complicações , Linfoma de Burkitt/diagnóstico , Edema/etiologia , Face , Cefaleia/etiologia , Obstrução Nasal/etiologia , Adolescente , Linfoma de Burkitt/patologia , Criança , Pré-Escolar , Exoftalmia/etiologia , Feminino , Humanos , Lactente , Neoplasias Renais/etiologia , Neoplasias Hepáticas/etiologia , Masculino , Maxila , Nasofaringe , Neoplasias Pancreáticas/etiologia , Seios Paranasais/patologia
10.
Nat Commun ; 10(1): 820, 2019 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-30778055

RESUMO

Stimulation of the B cell antigen receptor (BCR) triggers signaling pathways that promote the differentiation of B cells into plasma cells. Despite the pivotal function of BCR in B cell activation, the organization of the BCR on the surface of resting and antigen-activated B cells remains unclear. Here we show, using STED super-resolution microscopy, that IgM-containing BCRs exist predominantly as monomers and dimers in the plasma membrane of resting B cells, but form higher oligomeric clusters upon stimulation. By contrast, a chronic lymphocytic leukemia-derived BCR forms dimers and oligomers in the absence of a stimulus, but a single amino acid exchange reverts its organization to monomers in unstimulated B cells. Our super-resolution microscopy approach for quantitatively analyzing cell surface proteins may thus help reveal the nanoscale organization of immunoreceptors in various cell types.


Assuntos
Linfócitos B/metabolismo , Membrana Celular/metabolismo , Microscopia de Fluorescência/métodos , Receptores de Antígenos de Linfócitos B/metabolismo , Linfoma de Burkitt/patologia , Linhagem Celular Tumoral , Humanos , Fragmentos Fab das Imunoglobulinas/genética , Fragmentos Fab das Imunoglobulinas/metabolismo , Imunoglobulina M/metabolismo , Leucemia Linfocítica Crônica de Células B/metabolismo , Leucemia Linfocítica Crônica de Células B/patologia , Multimerização Proteica , Receptores de Antígenos de Linfócitos B/genética
11.
Pesqui. bras. odontopediatria clín. integr ; 19(1): 4325, 01 Fevereiro 2019. tab, graf
Artigo em Inglês | LILACS, BBO - Odontologia | ID: biblio-997983

RESUMO

Objective: To determine the activity of anti-cancer and anti-proliferation of ethyl acetate fraction of ant nest plants (Myrmecodia pendans) in Burkitt's Lymphoma cancer cells. Material and Methods: The study was conducted in a pure laboratory experimental method using Burkitt's Lymphoma cancer cell culture. Gradual research begins with the determination, extraction and fractionation of ant nest plants, to test for proliferation barriers. Data analysis using two-way ANOVA followed by Post Hoc LSD test with a significance level of 95%. Pearson correlation test was conducted. Results: The results of testing the inhibition of Burkitt's Lymphoma cell proliferation with ethyl acetate extract treatment showed that there was inhibition of cell growth based on the concentration given, starting from the lowest concentration of 15.625 µg/mL. Likewise, the incubation time factor of 24, 48, and 72 hours showed that the longer the incubation time, the greater the inhibition of cell growth. Antiproliferation analysis of flavonoid ethyl acetate extract based on concentration and incubation time on absorption of optical density Burkitt's Lymphoma was statistically significant (p = 0.00). Conclusion: Ant nest ethyl acetate extract has the effect of proliferation inhibition on Burkitt's lymphoma cells.


Assuntos
Plantas Medicinais , Linfoma de Burkitt/patologia , Preparações de Plantas/uso terapêutico , Neoplasias/diagnóstico , Antineoplásicos/uso terapêutico , Formigas , Terapias Complementares/métodos , Análise de Variância , Escala Fujita-Pearson , Indonésia
12.
Int J Hematol ; 109(4): 483-490, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30701466

RESUMO

We undertook a retrospective study using the national registry data of hematopoietic stem cell transplantation (HSCT) in Japan to investigate the effect of graft source, particularly autologous or allogeneic tissue, on the treatment outcome in patients aged less than 18 years with relapsed or refractory B-cell non-Hodgkin lymphoma (B-NHL). Survival analysis was conducted on 31 autologous HSCT (auto-HSCT) and 48 allogeneic HSCT (allo-HSCT) recipients between 1990 and 2013. The 5-year survival rates were significantly lower for allo-HSCT compared to auto-HSCT recipients (32% vs. 55%; P = 0.036). Multivariate analysis of survival rates identified allogeneic graft, Burkitt histology, and lack of response to chemotherapy as poor prognostic factors for survival. The cumulative incidence of treatment-related mortality (TRM) was significantly higher in allo-HSCT compared to auto-HSCT recipients (P = 0.017), explaining the difference in survival rates. In patients with Burkitt lymphoma (BL), overall survival was significantly inferior in the group of patients undergoing HSCT within 12 months from the initial diagnosis (P = 0.039). These data indicate that treatment outcomes for HSCT in children and adolescents with B-NHL were better in autograft recipients, suggesting that greater attention should be paid to the risk of TRM, especially after allografts, for patients with BL.


Assuntos
Linfoma de Burkitt/genética , Linfoma de Burkitt/mortalidade , Transplante de Células-Tronco Hematopoéticas , Sistema de Registros , Adolescente , Aloenxertos , Autoenxertos , Linfoma de Burkitt/patologia , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Humanos , Lactente , Japão , Masculino , Recidiva , Fatores de Risco , Taxa de Sobrevida
13.
Ann Nucl Med ; 33(4): 280-287, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30788775

RESUMO

OBJECTIVE: Burkitt's lymphoma (BL) is an aggressive lymphoma sub-type with high 18F-FDG avidity, but no well established evidence of PET/CT's role in treatment evaluation or prognosis is currently available. The prognostic role of visual analysis and Deauville criteria for BL have already been demonstrated, while the potential usefulness of semi-quantitative PET/CT features remains unclear, especially the value of the rate of reduction in metabolic tumor volume (MTV) and total lesion glycolysis (TLG). The aim of this retrospective study was to investigate whether ΔMTV and ΔTLG can predict treatment response at the end of therapy and prognosis in BL. METHODS: We retrospectively included 61 patients (mean age 61; 40 male, 21 female) who underwent baseline, interim and end-of-treatment 18F-FDG PET/CT. The PET/CT images were analyzed visually and semi-quantitatively by measuring total metabolic tumor volume (MTV) and total lesion glycolysis (TLG) for every scan. Then we calculated volume changes based on the percentage of MTV and TLG reduction between the baseline and interim PET (ΔMTVi and ΔTLGi) and between baseline and end-of-treatment PET/CT (ΔMTVeot and ΔTLGeot) and correlated them with clinical response and progression-free survival (PFS) and overall survival (OS). Survival curves were plotted according to the Kaplan-Meier method. RESULTS: Forty patients had a complete response and 21 patients a partial response on interim 18F-FDG PET/CT. At end of treatment, 45 had a complete response, 11 partial response and 5 disease progression. At a median follow-up of 43 months, relapse/progression occurred in 18 patients and death in 11. ΔMTV and ΔTLG values were significantly higher in patients with complete response compared to no complete response. ΔMTVeot and ΔTLGeot were demonstrated to be independent prognostic factors for both PFS and OS, while ΔMTVi and ΔTLGi were not related to survival. CONCLUSIONS: Metabolic tumor features (ΔMTV and ΔTLG) were significantly correlated with response to treatment and long-term outcome in BL.


Assuntos
Linfoma de Burkitt/diagnóstico , Linfoma de Burkitt/metabolismo , Glicólise , Carga Tumoral , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Linfoma de Burkitt/diagnóstico por imagem , Linfoma de Burkitt/patologia , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Prognóstico , Estudos Retrospectivos , Adulto Jovem
14.
Blood ; 133(12): 1313-1324, 2019 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-30617194

RESUMO

Although generally curable with intensive chemotherapy in resource-rich settings, Burkitt lymphoma (BL) remains a deadly disease in older patients and in sub-Saharan Africa. Epstein-Barr virus (EBV) positivity is a feature in more than 90% of cases in malaria-endemic regions, and up to 30% elsewhere. However, the molecular features of BL have not been comprehensively evaluated when taking into account tumor EBV status or geographic origin. Through an integrative analysis of whole-genome and transcriptome data, we show a striking genome-wide increase in aberrant somatic hypermutation in EBV-positive tumors, supporting a link between EBV and activation-induced cytidine deaminase (AICDA) activity. In addition to identifying novel candidate BL genes such as SIN3A, USP7, and CHD8, we demonstrate that EBV-positive tumors had significantly fewer driver mutations, especially among genes with roles in apoptosis. We also found immunoglobulin variable region genes that were disproportionally used to encode clonal B-cell receptors (BCRs) in the tumors. These include IGHV4-34, known to produce autoreactive antibodies, and IGKV3-20, a feature described in other B-cell malignancies but not yet in BL. Our results suggest that tumor EBV status defines a specific BL phenotype irrespective of geographic origin, with particular molecular properties and distinct pathogenic mechanisms. The novel mutation patterns identified here imply rational use of DNA-damaging chemotherapy in some patients with BL and targeted agents such as the CDK4/6 inhibitor palbociclib in others, whereas the importance of BCR signaling in BL strengthens the potential benefit of inhibitors for PI3K, Syk, and Src family kinases among these patients.


Assuntos
Biomarcadores Tumorais/genética , Linfoma de Burkitt/genética , Infecções por Vírus Epstein-Barr/complicações , Genes de Imunoglobulinas , Genoma Humano , Mutação , Transcriptoma , Adolescente , Adulto , Linfoma de Burkitt/patologia , Linfoma de Burkitt/virologia , Criança , Pré-Escolar , Estudos de Coortes , Citidina Desaminase/genética , Infecções por Vírus Epstein-Barr/genética , Infecções por Vírus Epstein-Barr/virologia , Feminino , Seguimentos , Herpesvirus Humano 4/isolamento & purificação , Humanos , Lactente , Recém-Nascido , Masculino , Fenótipo , Prognóstico , Adulto Jovem
15.
Int J Pediatr Otorhinolaryngol ; 118: 160-164, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30639969

RESUMO

OBJECTIVE: To examine the survival of pediatric tonsillar cancer patients and review a rare case of pediatric tonsillar cancer. METHODS: Pediatric patients in the Surveillance, Epidemiology, and End Results (SEER) database were included from 1973 to 2014 based on a diagnosis of tonsillar malignancy using the ICD O-3 tonsil primary site codes of: C09.0, C09.1, C09.8, and C09.9. Patients were included from birth-18 years. Survival analysis was performed using Kaplan-Meier analysis. Additionally, a case of pediatric natural killer (NK) cell tonsillar lymphoma diagnosed and treated at the Nemours Children's hospital in Orlando, Florida is presented. RESULTS: One hundred forty-one cases of tonsil cancer were identified. The mean age at diagnosis was 9.9 years (SD: 5.1, range: 0.0 (months)-18.0). Ninety five (67.4%) patients were male and 116 (82.3%) had unilateral malignancies. Burkitt lymphoma (32.6%) followed by diffuse large B-cell lymphoma (DLBCL) (27.0%) were the two most common histological types of tonsillar cancers. 79.4% of patients received chemotherapy and 81.6% received surgery as a part of their care. The 5-year disease-specific survival rate was >90% for patient cohorts diagnosed from 1984 to 1993, 1994-2003, and 2004-2014 as compared to 64% for patients diagnosed from 1973 to 1983 (p = 0.01). CONCLUSIONS: Survival rates for pediatric patients with tonsillar cancer are excellent. Pediatric primary tonsil cancer occurred most commonly in adolescent males and usually presents as a unilateral mass. Lymphoma remains the predominant histological type of cancer. Most patients are likely to receive surgery and chemotherapy.


Assuntos
Linfoma de Burkitt/mortalidade , Linfoma de Burkitt/terapia , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/terapia , Neoplasias Tonsilares/mortalidade , Neoplasias Tonsilares/terapia , Adolescente , Antineoplásicos/uso terapêutico , Linfoma de Burkitt/patologia , Criança , Pré-Escolar , Bases de Dados Factuais , Feminino , Humanos , Recém-Nascido , Estimativa de Kaplan-Meier , Linfoma Difuso de Grandes Células B/patologia , Masculino , Programa de SEER , Taxa de Sobrevida , Tonsilectomia , Estados Unidos/epidemiologia
16.
Blood ; 133(9): 962-966, 2019 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-30567752

RESUMO

The new recently described provisional lymphoma category Burkitt-like lymphoma with 11q aberration comprises cases similar to Burkitt lymphoma (BL) on morphological, immunophenotypic and gene-expression levels but lacking the IG-MYC translocation. They are characterized by a peculiar imbalance pattern on chromosome 11, but the landscape of mutations is not yet described. Thus, we investigated 15 MYC-negative Burkitt-like lymphoma with 11q aberration (mnBLL,11q,) cases by copy-number analysis and whole-exome sequencing. We refined the regions of 11q imbalance and identified the INO80 complex-associated gene NFRKB as a positional candidate in 11q24.3. Next to recurrent gains in 12q13.11-q24.32 and 7q34-qter as well as losses in 13q32.3-q34, we identified 47 genes recurrently affected by protein-changing mutations (each ≥3 of 15 cases). Strikingly, we did not detect recurrent mutations in genes of the ID3-TCF3 axis or the SWI/SNF complex that are frequently altered in BL, or in genes frequently mutated in germinal center-derived B-cell lymphomas like KMT2D or CREBBP An exception is GNA13, which was mutated in 7 of 15 cases. We conclude that the genomic landscape of mnBLL,11q, differs from that of BL both at the chromosomal and mutational levels. Our findings implicate that mnBLL,11q, is a lymphoma category distinct from BL at the molecular level.


Assuntos
Biomarcadores Tumorais/genética , Linfoma de Burkitt/classificação , Linfoma de Burkitt/genética , Aberrações Cromossômicas , Cromossomos Humanos Par 11/genética , Mutação , Adolescente , Adulto , Linfoma de Burkitt/patologia , Criança , Pré-Escolar , DNA Helicases/genética , Proteínas de Ligação a DNA/genética , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteínas Proto-Oncogênicas c-myc/genética , Estudos Retrospectivos , Adulto Jovem
17.
Eur J Nucl Med Mol Imaging ; 46(1): 87-96, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30276438

RESUMO

PURPOSE: Burkitt's lymphoma (BL) is an aggressive lymphoma subtype with high 18F-FDG avidity at 18F-FDG-PET/CT, but no validated criteria for PET/CT in treatment evaluation or prediction of outcome in BL are available. The aim of our study was to investigate whether the metabolic baseline PET/CT parameters can predict treatment response and prognosis in BL. MATERIALS AND METHODS: We retrospectively enrolled 65 patients who underwent baseline 18F-FDG-PET/CT, interim and end of treatment PET/CT. The PET images were analyzed visually and semi-quantitatively by measuring the maximum standardized uptake value body weight (SUVbw), the maximum standardized uptake value lean body mass (SUVlbm), the maximum standardized uptake value body surface area (SUVbsa), lesion to liver SUVmax ratio (L-L SUV R), lesion to blood-pool SUVmax ratio (L-BP SUV R), total metabolic tumor volume (tMTV) and total lesion glycolysis (TLG). Survival curves were plotted according to the Kaplan-Meier method. RESULTS: At a median follow-up of 40 months, the median PFS and OS were 34 and 39 months. MTV and TLG were significantly higher in patients with partial response compared to complete response group at end of treatment, while no significant differences were found at interim. Other metabolic PET/CT parameters were not related to treatment response. MTV and TLG were demonstrated to be independent prognostic factors for both PFS and OS; instead SUVbw, SUVlbm, SUVbsa, L-L SUV R and L-BP SUV R were not related to outcome survival. CONCLUSIONS: Metabolic tumour features (MTV and TLG) were significantly correlated with response to treatment and long-term outcome.


Assuntos
Linfoma de Burkitt/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/normas , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Linfoma de Burkitt/patologia , Feminino , Fluordesoxiglucose F18 , Glicólise , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Compostos Radiofarmacêuticos
18.
Int J Pediatr Otorhinolaryngol ; 117: 171-174, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30579076

RESUMO

OBJECTIVE: To evaluate the incidence of tonsil and adenoid malignancy in pediatric patients in Israel compared to the known literature and to revisit the common practice of routine histopathologic examination of tonsils and adenoids. METHODS: Analysis of the Israel National Cancer Registry data on pediatric tonsil and adenoid malignancies between the years 2005 and 2015, and a systematic literature review of all relevant articles that reported on malignancies amongst pediatric patients who underwent tonsillectomy with or without adenoidectomy. RESULTS: Only seven cases of tonsillar malignancies were documented out of 152,352 (0.0052%) surgeries in the pediatric population. All malignancies were lymphoproliferative and mainly Burkitt's lymphoma. In our medical center no malignancy was found in 2165 patients in the same age groups and time period. We found the incidence of tonsillar malignancy in Israel to be significantly lower (p = 0.013) compared to the previously described literature. CONCLUSION: The incidence of malignancy in routine histopathological examination of tonsils and adenoids is Israel is very low when compared to the known literature. According to these results, we suggest that routine histopathological examination of all such samples is not clinically justified.


Assuntos
Linfoma de Burkitt/epidemiologia , Neoplasias Tonsilares/epidemiologia , Adenoidectomia , Tonsila Faríngea/patologia , Adolescente , Linfoma de Burkitt/patologia , Criança , Pré-Escolar , Humanos , Incidência , Achados Incidentais , Lactente , Recém-Nascido , Israel/epidemiologia , Sistema de Registros , Estudos Retrospectivos , Neoplasias Tonsilares/patologia , Tonsilectomia
19.
Cell Death Dis ; 10(1): 8, 2018 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-30584254

RESUMO

An intensive short-term chemotherapy regimen has substantially prolonged the overall survival of Burkitt's lymphoma (BL) patients, which has been further improved by addition of rituximab. However, the inevitable development of resistance to rituximab and the toxicity of chemotherapy remain obstacles. We first prepared two BL cell lines resistant to rituximab-mediated CDC. Using a phosphorylation antibody microarray, we revealed that PI3K/AKT pathway contained the most phosphorylated proteins/hits, while apoptosis pathway that may be regulated by PKC displayed the greatest fold enrichment in the resistant cells. The PI3K/AKT inhibitor IPI-145 failed to reverse the resistance. In contrast, the pan-PKC inhibitor midostaurin exhibited potent antitumor activity in both original and resistant cells, alone or in combination with rituximab. Notably, midostaurin promoted apoptosis by reducing the phosphorylation of PKC and consequently of downstream Bad, Bcl-2 and NF-κB. Therefore, midostaurin improved rituximab activity by supplementing pro-apoptotic effects. In vivo, midostaurin alone powerfully prolonged the survival of mice bearing the resistant BL cells compared to rituximab alone treatments. Addition of midostaurin to rituximab led to dramatically improved survival compared to rituximab but not midostaurin monotherapy. Our findings call for further evaluation of midostaurin alone or in combination with rituximab in treating resistant BL in particular.


Assuntos
Apoptose/efeitos dos fármacos , Linfoma de Burkitt/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Rituximab/farmacologia , Estaurosporina/análogos & derivados , Animais , Linfoma de Burkitt/metabolismo , Linfoma de Burkitt/patologia , Linhagem Celular Tumoral , Feminino , Humanos , Camundongos , Camundongos SCID , Proteínas de Neoplasias/metabolismo , Estaurosporina/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
20.
Stem Cell Res Ther ; 9(1): 353, 2018 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-30572947

RESUMO

A 27-year-old male with HIV-associated naïve and high-risk Burkitt's lymphoma sequentially received short-term, high-dose non-myeloablative chemotherapy and autologous CD34-positive stem cell transfusion in the setting of combined antiretroviral therapy (cART). Prompt hematopoietic recovery was observed after 2 weeks and clinical remission from Burkitt's lymphoma within approximately 30 months after transplantation. The HIV RNA load was inhibited persistently, and drug resistance was not observed. The CD4+ T cell count approached 323 cells/µL in a recent follow-up study. This case suggests that the use of intensive non-myeloablative chemotherapy with transplantation, combined with antiretroviral therapy, in HIV-related naive and high-risk Burkitt's lymphoma was tolerated and safe.


Assuntos
Antirretrovirais/uso terapêutico , Linfoma de Burkitt/tratamento farmacológico , Linfoma de Burkitt/terapia , Infecções por HIV/complicações , Transplante de Células-Tronco Hematopoéticas/métodos , Transplante Autólogo/métodos , Adulto , Antirretrovirais/farmacologia , Linfoma de Burkitt/patologia , Terapia Combinada , Infecções por HIV/patologia , Humanos , Masculino , Condicionamento Pré-Transplante
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