Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 6.655
Filtrar
1.
Medicine (Baltimore) ; 99(15): e19850, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32282749

RESUMO

RATIONALE: Methotrexate-associated lymphoproliferative disorder (MTX-LPD) is a serious complication in patients treated using methotrexate. It occasionally develops in extra-nodal sites, but rarely in the central nervous system (CNS) or in 2 different sites at the same time. We present the rare case of a patient with rheumatoid arthritis who developed lymphoma in the CNS and stomach during MTX therapy. PATIENT CONCERNS: A 75-year-old Japanese man with rheumatoid arthritis who received methotrexate was admitted to our hospital because of gait ataxia and anorexia. DIAGNOSES: Imaging findings and biopsy led to a diagnosis of 2 different types of MTX-LPD in the central nervous system and stomach. INTERVENTIONS: The lesion in his stomach improved after methotrexate withdrawal, whereas the cerebellar mass required high-dose methotrexate and rituximab therapy. OUTCOMES: Complete remission has been maintained for the 2 years following the initiation of chemotherapy. LESSONS: In patients with RA who receive MTX and develop new neurological symptoms, CNS lymphoma as an MTX-LPD may be considered as a differential diagnosis.


Assuntos
Antimetabólitos Antineoplásicos/efeitos adversos , Artrite Reumatoide/complicações , Neoplasias do Sistema Nervoso Central/patologia , Linfoma/induzido quimicamente , Metotrexato/efeitos adversos , Idoso , Antimetabólitos Antineoplásicos/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/diagnóstico por imagem , Diagnóstico Diferencial , Endoscopia do Sistema Digestório/métodos , Feminino , Marcha Atáxica/diagnóstico , Marcha Atáxica/etiologia , Humanos , Linfoma/diagnóstico , Linfoma/tratamento farmacológico , Imagem por Ressonância Magnética , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Rituximab/uso terapêutico , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Resultado do Tratamento
2.
Phys Ther ; 100(3): 509-522, 2020 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-32044966

RESUMO

BACKGROUND: Glucocorticoids used to treat childhood leukemia and lymphoma can result in osteonecrosis, leading to physical dysfunction and pain. Improving survival rates warrants research into long-term outcomes among this population. OBJECTIVE: The objective of this study was to compare the physical function and quality of life (QOL) of survivors of childhood cancer who had an osteonecrosis history with that of survivors who had no osteonecrosis history and with that of people who were healthy (controls). DESIGN: This was a cross-sectional study. METHODS: This study included St Jude Lifetime Cohort Study participants who were ≥ 10 years from the diagnosis of childhood leukemia or lymphoma and ≥ 18 years old; 135 had osteonecrosis (52.5% men; mean age = 27.7 [SD = 6.08] years) and 1560 had no osteonecrosis history (52.4% men; mean age = 33.3 [SD = 8.54] years). This study also included 272 people who were from the community and who were healthy (community controls) (47.7% men; mean age = 35.1 [SD = 10.46] years). The participants completed functional assessments and questionnaires about QOL. RESULTS: Survivors with osteonecrosis scored lower than other survivors and controls for dorsiflexion strength (mean score = 16.50 [SD = 7.91] vs 24.17 [SD = 8.61] N·m/kg) and scored lower than controls for flexibility with the sit-and-reach test (20.61 [SD = 9.70] vs 23.96 [SD = 10.73] cm), function on the Physical Performance Test (mean score = 22.73 [SD = 2.05] vs 23.58 [SD = 0.88]), and mobility on the Timed "Up & Go" Test (5.66 [SD = 2.25] vs 5.12 [SD = 1.28] seconds). Survivors with hip osteonecrosis requiring surgery scored lower than survivors without osteonecrosis for dorsiflexion strength (13.75 [SD = 8.82] vs 18.48 [SD = 9.04] N·m/kg), flexibility (15.79 [SD = 8.93] vs 20.37 [SD = 10.14] cm), and endurance on the 6-minute walk test (523.50 [SD = 103.00] vs 572.10 [SD = 102.40] m). LIMITATIONS: Because some eligible survivors declined to participate, possible selection bias was a limitation of this study. CONCLUSIONS: Survivors of childhood leukemia and lymphoma with and without osteonecrosis demonstrated impaired physical performance and reported reduced QOL compared with controls, with those requiring surgery for osteonecrosis most at risk for impairments. It may be beneficial to provide strengthening, flexibility, and endurance interventions for patients who have pediatric cancer and osteonecrosis for long-term function.


Assuntos
Sobreviventes de Câncer , Leucemia/tratamento farmacológico , Linfoma/tratamento farmacológico , Osteonecrose/fisiopatologia , Desempenho Físico Funcional , Qualidade de Vida , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Estudos Transversais , Feminino , Glucocorticoides/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Força Muscular , Osteonecrose/induzido quimicamente , Osteonecrose/cirurgia , Amplitude de Movimento Articular , Participação Social , Teste de Caminhada
3.
Dtsch Med Wochenschr ; 145(1): 36-39, 2020 01.
Artigo em Alemão | MEDLINE | ID: mdl-31914467

RESUMO

HISTORY AND CLINICAL FINDINGS: A 53-year-old male presented with massive pruritus, whole-body exanthema, generalized muscle pain, and exercise dyspnoea NYHA II. FINDINGS AND DIAGNOSIS: Further hematologic examination lead to diagnosis of myeloid and lymphoid neoplasia with eosinophilia (MLN-EO) with FIPL1L1-PDGFRA fusion gene. An echocardiographic examination revealed a thrombus in the right ventricle. Magnetic resonance imaging (MRI) showed an extensive intracavitary thrombus extending from the apex to the right ventricular outflow tract. THERAPY AND COURSE: Oral anticoagulation with phenprocoumon and a targeted therapy with imatinib were initiated. Follow-up at 11- and 23-months revealed diminishing of the thrombus. Further follow-up did not show any complications. CONCLUSIONS: In summary, Loeffler's endocarditis caused by a myeloid and lymphoid neoplasm associated with eosinophilia and abnormalities of FIP1L1-PDGFRA rearrangement could be treated successfully with oral anticoagulation therapy and the tyrosine-kinase inhibitor imatinib.


Assuntos
Eosinofilia/complicações , Síndrome Hipereosinofílica/complicações , Mesilato de Imatinib/uso terapêutico , Linfoma , Antineoplásicos/uso terapêutico , Humanos , Linfoma/complicações , Linfoma/tratamento farmacológico , Masculino , Pessoa de Meia-Idade
4.
Proc Natl Acad Sci U S A ; 117(3): 1666-1677, 2020 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-31911474

RESUMO

Major efforts are underway to identify agents that can potentiate effects of immune checkpoint inhibition. Here, we show that ascorbic acid (AA) treatment caused genomewide demethylation and enhanced expression of endogenous retroviral elements in lymphoma cells. AA also increased 5-hydroxymethylcytosine (5hmC) levels of CD8+ T cells and enhanced their cytotoxic activity in a lymphoma coculture system. High-dose AA treatment synergized with anti-PD1 therapy in a syngeneic lymphoma mouse model, resulting in marked inhibition of tumor growth compared with either agent alone. Analysis of the intratumoral epigenome revealed increased 5hmC with AA treatment, consistent with in vitro findings. Analysis of the tumor immune microenvironment revealed that AA strikingly increased intratumoral infiltration of CD8+ T cells and macrophages, suggesting enhanced tumor immune recognition. The combination treatment markedly enhanced intratumoral infiltration of macrophages and CD8+ T lymphocytes, granzyme B production by cytotoxic cells (cytotoxic T cells and natural killer cells), and interleukin 12 production by antigen-presenting cells compared with single-agent anti-PD1. These data indicate that AA potentiates anti-PD1 checkpoint inhibition through synergistic mechanisms. The study provides compelling rationale for testing combinations of high-dose AA and anti-PD1 agents in patients with aggressive B cell lymphoma as well as in preclinical models of other malignancies.


Assuntos
Anticorpos Monoclonais/farmacologia , Antineoplásicos/farmacologia , Ácido Ascórbico/administração & dosagem , Linfoma/tratamento farmacológico , 5-Metilcitosina/análogos & derivados , Animais , Antígeno B7-H1 , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Terapia Combinada , Modelos Animais de Doenças , Sinergismo Farmacológico , Feminino , Granzimas , Imunoterapia , Camundongos , Camundongos Endogâmicos BALB C , Receptor de Morte Celular Programada 1/efeitos dos fármacos , Receptor de Morte Celular Programada 1/metabolismo , Microambiente Tumoral/efeitos dos fármacos
6.
Am Fam Physician ; 101(1): 34-41, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31894937

RESUMO

Lymphoma is a group of malignant neoplasms of lymphocytes with more than 90 subtypes. It is traditionally classified broadly as non-Hodgkin or Hodgkin lymphoma. Approximately 82,000 new U.S. patients are diagnosed with lymphoma annually. Any tobacco use and obesity are major modifiable risk factors, with genetic, infectious, and inflammatory etiologies also contributing. Lymphoma typically presents as painless adenopathy, with systemic symptoms of fever, unexplained weight loss, and night sweats occurring in more advanced stages of the disease. An open lymph node biopsy is preferred for diagnosis. The Lugano classification system incorporates symptoms and the extent of the disease as shown on positron emission tomography/computed tomography to stage lymphoma, which is then used to determine treatment. Chemotherapy treatment plans differ between the main subtypes of lymphoma. Non-Hodgkin lymphoma is treated with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) with or without rituximab (R-CHOP), bendamustine, and lenalidomide. Hodgkin lymphoma is treated with combined chemotherapy with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine), Stanford V (a chemotherapy regimen consisting of mechlorethamine, doxorubicin, vinblastine, vincristine, bleomycin, etoposide, and prednisone), or BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) with radiotherapy. Subsequent chemotherapy toxicities include neuropathy, cardiotoxicity, and secondary cancers such as lung and breast, and should be considered in the shared decision-making process to select a treatment regimen. Once remission is achieved, patients need routine surveillance to monitor for complications and relapse, in addition to age-appropriate screenings recommended by the U.S. Preventive Services Task Force. Patients should receive a 13-valent pneumococcal conjugate vaccine followed by a 23-valent pneumococcal polysaccharide vaccine at least eight weeks later with additional age-appropriate vaccinations because lymphoma is an immunosuppressive condition. Household contacts should also be current with their immunizations.


Assuntos
Linfoma/diagnóstico , Linfoma/tratamento farmacológico , Adulto , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Biópsia , Medicina Baseada em Evidências , Feminino , Humanos , Linfoma/mortalidade , Linfoma/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Fatores de Risco , Estados Unidos/epidemiologia
7.
Clin Oral Investig ; 24(1): 133-140, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31041576

RESUMO

OBJECTIVES: To investigate signs of infection and infection-related complications of apical periodontitis (AP) in patients who underwent chemotherapy for lymphoma. MATERIALS AND METHODS: Data were collected retrospectively from the dental and medical records of patients receiving chemotherapy for lymphoma. Based on the findings from a dental evaluation made in conjunction with chemotherapy, the patients were divided into two groups, patients with or without teeth with AP. RESULTS: Eighty-six of the 213 patients had one or more teeth with AP and received no planned dental treatment for this condition, while 127 patients had no AP-affected teeth. During chemotherapy, seven patients (8%) developed local symptoms related to teeth with AP, while no patients in the control group developed symptoms of AP. No significant differences were found with respect to the administration of antibiotics related to dental infection or hospital admission events due to fever or infection, between the group with AP and the group without AP. CONCLUSIONS: AP is a common finding and exacerbation seems more common in patients diagnosed with chronic AP than in patients without chronic AP. The presence of chronic AP in patients treated with chemotherapy for lymphoma is not linked to additional medical complications that require hospital admission owing to fever/infection. CLINICAL RELEVANCE: Knowledge regarding infection-related complications of AP in patients with lymphoma treated with chemotherapy will guide clinical decision-making by identifying those patients who warrant treatment. This will allow dental interventions to be postponed until completion of chemotherapy, without serious medical complications. The results of this study serve as a basis for larger prospective studies.


Assuntos
Antineoplásicos/uso terapêutico , Linfoma/tratamento farmacológico , Periodontite Periapical , Protocolos de Quimioterapia Combinada Antineoplásica , Bleomicina , Dacarbazina , Doxorrubicina , Feminino , Doença de Hodgkin , Humanos , Masculino , Estudos Prospectivos , Estudos Retrospectivos , Tratamento do Canal Radicular , Vimblastina
8.
Nat Rev Clin Oncol ; 17(3): 147-167, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31848460

RESUMO

T cells genetically engineered to express chimeric antigen receptors (CARs) have proven - and impressive - therapeutic activity in patients with certain subtypes of B cell leukaemia or lymphoma, with promising efficacy also demonstrated in patients with multiple myeloma. Nevertheless, various barriers restrict the efficacy and/or prevent the widespread use of CAR T cell therapies in these patients as well as in those with other cancers, particularly solid tumours. Key challenges relating to CAR T cells include severe toxicities, restricted trafficking to, infiltration into and activation within tumours, suboptimal persistence in vivo, antigen escape and heterogeneity, and manufacturing issues. The evolution of CAR designs beyond the conventional structures will be necessary to address these limitations and to expand the use of CAR T cells to a wider range of malignancies. Investigators are addressing the current obstacles with a wide range of engineering strategies in order to improve the safety, efficacy and applicability of this therapeutic modality. In this Review, we discuss the innovative designs of novel CAR T cell products that are being developed to increase and expand the clinical benefits of these treatments in patients with diverse cancers.


Assuntos
Terapia Baseada em Transplante de Células e Tecidos , Neoplasias/tratamento farmacológico , Receptores de Antígenos de Linfócitos T/uso terapêutico , Receptores de Antígenos Quiméricos/uso terapêutico , Engenharia Celular , Humanos , Linfoma/tratamento farmacológico , Linfoma/imunologia , Neoplasias/genética , Neoplasias/imunologia , Receptores de Antígenos de Linfócitos T/genética , Linfócitos T/imunologia
9.
Anticancer Res ; 39(10): 5703-5707, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570470

RESUMO

BACKGROUND/AIM: Anthracyclines, such as doxorubicin, though widely used in anticancer therapy, they are associated with cardiotoxic side-effects. The aim of this trial was to investigate long-term follow-up cardiotoxicity findings in patients treated with doxorubicin and concomitant metoprolol or enalapril 10 years earlier. PATIENTS AND METHODS: Overall, 147 patients were randomized into the treatment arms. A total of 125 patients treated with doxorubicin without evidence of heart disease at the start of chemotherapy were analyzed. They were followed-up for up to 10 years after treatment start. RESULTS AND CONCLUSION: A total of 47 patients completed the follow-up and 21 patients died, none due to cardiotoxicity events. Clinical signs of heart failure were not seen in any patients and no statistically significant differences between baseline and 10-year findings were seen for echocardiographic variables. No evidence of long-term cardiotoxicity was seen and nor metoprolol or enalapril offered an additional benefit.


Assuntos
Antibióticos Antineoplásicos/efeitos adversos , Cardiotoxicidade/prevenção & controle , Doxorrubicina/efeitos adversos , Enalapril/uso terapêutico , Linfoma/tratamento farmacológico , Metoprolol/uso terapêutico , Adolescente , Antraciclinas/uso terapêutico , Antibióticos Antineoplásicos/uso terapêutico , Cardiotoxicidade/etiologia , Doxorrubicina/uso terapêutico , Ecocardiografia/métodos , Feminino , Insuficiência Cardíaca/induzido quimicamente , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Masculino , Estudos Prospectivos
10.
J Cancer Res Clin Oncol ; 145(12): 3067-3073, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31563974

RESUMO

BACKGROUND: The combination of dexamethasone, high-dose cytarabine, and cisplatin (DHAP) is an established salvage regimen for lymphoma patients. We hypothesized that a modified administration schedule for cisplatin and cytarabine results in lower toxicity and improved efficacy. METHODS: We retrospectively analysed 119 patients with relapsed or refractory, aggressive, or indolent B-cell lymphomas, mantle-cell lymphomas, peripheral T-cell lymphomas, or Hodgkin's lymphomas who were treated with the modified DHAP (mDHAP) regimen (dexamethasone 40 mg 15 min-i.v. infusion, days 1-4; cytarabine 2 × 0.5 g/m2 1 h-i.v. infusion, days 1-4; cisplatin 25 mg/m2 24 h-i.v. infusion, days 1-4). Responding and eligible patients underwent stem-cell transplantation. RESULTS: In total, 185 treatment cycles were evaluable. Severe myelosuppression was the main toxicity occurring in 90% of the cycles. Febrile neutropenia or documented infection was found in less than 40%. Two patients died related to treatment (TRM, 1.7%). Nephrotoxicity did not exceed CTC grade 3, which occurred in four cycles only (2.2%). Complete (CR) or partial (PR) responses after mDHAP were documented in 16% and 39% (overall response rate 55%). Harvest of autologous stem cells was successful in 94 (79%) patients and 85 patients (71%) proceeded to stem-cell transplantation. The median overall and progression-free survival was 50.8 and 25.8 months. CONCLUSIONS: An improvement in efficacy could not be observed after modified DHAP regimen; however, manageable toxicity and reduced renal complications suggest further investigation. The study, however, also underlines the need for new concepts in the management of advanced and high-risk lymphomas.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Adolescente , Adulto , Idoso , Cisplatino/uso terapêutico , Citarabina/uso terapêutico , Dexametasona/uso terapêutico , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Terapia de Salvação/métodos , Adulto Jovem
11.
Cancer Immunol Immunother ; 68(10): 1561-1572, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31494742

RESUMO

Preclinical and clinical studies have suggested that cancer treatment with antitumor antibodies induces a specific adaptive T cell response. A central role in this process has been attributed to CD4+ T cells, but the relevant T cell epitopes, mostly derived from non-mutated self-antigens, are largely unknown. In this study, we have characterized human CD20-derived epitopes restricted by HLA-DR1, HLA-DR3, HLA-DR4, and HLA-DR7, and investigated whether T cell responses directed against CD20-derived peptides can be elicited in human HLA-DR-transgenic mice and human samples. Based on in vitro binding assays to recombinant human MHC II molecules and on in vivo immunization assays in H-2 KO/HLA-A2+-DR1+ transgenic mice, we have identified 21 MHC II-restricted long peptides derived from intracellular, membrane, or extracellular domains of the human non-mutated CD20 protein that trigger in vitro IFN-γ production by PBMCs and splenocytes from healthy individuals and by PBMCs from follicular lymphoma patients. These CD20-derived MHC II-restricted peptides could serve as a therapeutic tool for improving and/or monitoring anti-CD20 T cell activity in patients treated with rituximab or other anti-CD20 antibodies.


Assuntos
Antígenos CD20/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfoma/tratamento farmacológico , Animais , Feminino , Cadeias HLA-DRB1/imunologia , Humanos , Interferon gama/biossíntese , Linfoma/imunologia , Camundongos , Rituximab/uso terapêutico
12.
Med Sci Monit ; 25: 6563-6573, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31473762

RESUMO

BACKGROUND The aim of this study was to examine the effects and mechanisms of tenacigenin B in lymphoma treatment by in vitro and in vivo experiment. MATERIAL AND METHODS Raji cells were treated by difference methods. Measuring the cell proliferation of difference groups was done by MTT assay; cell apoptosis and cell cycle of difference groups were evaluated by flow cytometer; relative mRNA expression was evaluated by real-time polymerase chain reaction (RT-PCR), and relative protein expressions were measured by western blot assay in an in vitro study. In an in vivo study, we used a nude mice model to explore the anti-tumor effects and mechanism of tenacigenin B. Cell apoptosis was measured by TUNEL assay; relative protein expressions were evaluated by immunohistochemistry assay, and relative mRNA expression was evaluated by RT-PCR. In addition, the blood components of difference groups were measured. RESULTS Compared with the Normal control group, the cell proliferation rate was significantly downregulated, with cell apoptosis significantly increasing with G1 phase in the Drug group and the si-Aurora-A group (P<0.05, respectively). The PTEN, PI3K, AKT, P53, and P21 mRNA and protein expressions of the Drug group, the si-Aurora-A group, and the si-Aurora-A+Drug group were significantly different (P<0.01, respectively), The tumor volume and weight of the Drug group, the si-Aurora-A group, and the si-Aurora-A+Drug group were significantly suppressed compared with the Normal group (P<0.01, respectively). The positive apoptosis cell number in the Drug group, the si-Aurora-A group, and si-Aurora-A+Drug group were increased compared with that of Normal group (P<0.01, respectively). CONCLUSIONS Tenacigenin B had anti-tumor effects on lymphoma via regulation of Aurora-A in vitro and in vivo.


Assuntos
Antineoplásicos/uso terapêutico , Linfoma/tratamento farmacológico , Esteroides/uso terapêutico , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Linfoma/patologia , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Esteroides/farmacologia
13.
An. pediatr. (2003. Ed. impr.) ; 91(3): 189-198, sept. 2019. tab, ilus
Artigo em Espanhol | IBECS | ID: ibc-186730

RESUMO

Introducción: Se ha descrito la regeneración del timo tras la quimioterapia en niños con linfoma y, para evitar diagnosticar incorrectamente estos casos como recurrencias, los facultativos han de familiarizarse con la hiperplasia tímica de rebote (HTR) y tener en consideración su posible ocurrencia. Nuestro objetivo fue estimar la prevalencia de HTR en niños con linfoma tras la quimioterapia y evaluar las características clínicas, evolución y hallazgos de las pruebas de imagen mediante tomografía computarizada (TC) y la gammagrafía con galio 67 (GA-67). Pacientes y métodos: Estudio retrospectivo transversal, mediante la revisión de las historias clínicas de niños diagnosticados de linfoma, realizado en la Clínica Ambulatoria de Oncología Infantil del Centro de Oncología de Yeda, Arabia Saudita. Resultados: Se detectó HTR en el 51,9% de los pacientes con linfoma (14/27 pacientes). La HTR ocurrió una mediana de 2,5 meses tras finalizarse el tratamiento (rango: 2,0-4,25 meses). Los pacientes con HTR recibieron tratamientos significativamente más cortos, y no se observaron diferencias entre pacientes con y sin HTR en cuanto al sexo, la edad al diagnóstico, el tipo de linfoma o el tipo de tratamiento recibido. Todos los pacientes con HTR se encontraban asintomáticos y las pruebas rutinarias de laboratorio no evidenciaron alteraciones. La TC y la GA-67 fueron altamente sugestivas de HTR. Ninguno de los pacientes con HTR tuvieron recurrencias y la HTR se resolvió espontáneamente en una mediana de 6 meses (rango: 4,0-11,0 meses). Conclusión: Se detectó HTR en alrededor del 50% de los niños con linfoma tras completarse el tratamiento. La evaluación clínica, pruebas de laboratorio, TC y gammagrafía con GA-67 resultan útiles para identificar la HTR y descartar otras lesiones en otras localizaciones


Introduction: Thymic regrowth after chemotherapy treatment has been reported in children with lymphoma, and in order to avoid misdiagnosing these cases as relapses, physicians should become familiar with rebound (reactive) thymic hyperplasia (RTH) and remain aware of its possible occurrence. We aimed to estimate the prevalence of RTH in children with lymphoma after completion of chemotherapy and to evaluate the clinical characteristics, outcomes, and the findings of computed tomography (CT) and gallium-67 (GA-67) scans in these patients. Patients and methods: We conducted a retrospective cross-sectional study by reviewing the health records of children with a lymphoma diagnosis managed at an outpatient paediatric oncology clinic in Jeddah, Saudi Arabia. Results: Rebound thymic hyperplasia was detected in 51.9% of the lymphoma patients (14/27). It developed a median of 2.5 months after completion of chemotherapy (range, 2.0-4.25 months). Patients with RTH had significantly shorter treatment durations, and we found no significant differences between patients with and without RTH in sex, age at diagnosis, type of lymphoma or type of treatment received. All patients with RTH were asymptomatic, and routine laboratory tests did not detect any abnormalities in them. The findings of CT and GA-67 scans were highly suggestive of RTH. None of the patients with RTH had a recurrence, and RTH resolved spontaneously within a median of 6 months (range, 4.0-11.0). Conclusion: RTH was detected in ∼50% of children with lymphoma after completion of chemotherapy. A clinical evaluation and laboratory tests combined with imaging by CT and GA-67 can help identify RTH and rule out other lesions elsewhere


Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Criança , Antineoplásicos/efeitos adversos , Linfoma/tratamento farmacológico , Hiperplasia do Timo/diagnóstico por imagem , Antineoplásicos/administração & dosagem , Estudos Transversais , Radioisótopos de Gálio/administração & dosagem , Prevalência , Estudos Retrospectivos , Arábia Saudita , Hiperplasia do Timo/epidemiologia , Hiperplasia do Timo/etiologia , Fatores de Tempo , Tomografia Computadorizada de Emissão
14.
Int J Mol Sci ; 20(16)2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31405039

RESUMO

SUMO (Small Ubiquitin-related MOdifier) is a post-translational modifier of the ubiquitin family controlling the function and fate of thousands of proteins. SUMOylation is deregulated in various hematological malignancies, where it participates in both tumorigenesis and cancer cell response to therapies. This is the case for Acute Promyelocytic Leukemias (APL) where SUMOylation, and subsequent destruction, of the PML-RARα fusion oncoprotein are triggered by arsenic trioxide, which is used as front-line therapy in combination with retinoic acid to cure APL patients. A similar arsenic-induced SUMO-dependent degradation was also documented for Tax, a human T-cell lymphotropic virus type I (HTLV1) viral protein implicated in Adult T-cell Leukemogenesis. SUMOylation also participates in Acute Myeloid Leukemia (AML) response to both chemo- and differentiation therapies, in particular through its ability to regulate gene expression. In Multiple Myeloma, many enzymes of the SUMO pathway are overexpressed and their high expression correlates with lower response to melphalan-based chemotherapies. B-cell lymphomas overexpressing the c-Myc oncogene also overexpress most components of the SUMO pathway and are highly sensitive to SUMOylation inhibition. Targeting the SUMO pathway with recently discovered pharmacological inhibitors, alone or in combination with current therapies, might therefore constitute a powerful strategy to improve the treatment of these cancers.


Assuntos
Leucemia/metabolismo , Linfoma/metabolismo , Mieloma Múltiplo/metabolismo , Proteína SUMO-1/metabolismo , Animais , Antineoplásicos/uso terapêutico , Neoplasias Hematológicas/tratamento farmacológico , Neoplasias Hematológicas/metabolismo , Humanos , Leucemia/tratamento farmacológico , Linfoma/tratamento farmacológico , Terapia de Alvo Molecular , Mieloma Múltiplo/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Sumoilação/efeitos dos fármacos
15.
J Otolaryngol Head Neck Surg ; 48(1): 37, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31383004

RESUMO

BACKGROUND: Primary lymphoma of the oral cavity is a rare phenomenon. Herein we describe a unique presentation of lymphoma of the tongue which initially manifested as trigeminal neuralgia. CASE PRESENTATION: A 63-year-old female experienced a 10-month history of paresthesia and neuropathic pain involving the left tongue and mandibular area of her face. Investigations including imaging and biopsy revealed primary lymphoma of the tongue with extensive perineural spread. The patient underwent standard chemotherapy with complete radiological response, but minimal recovery of the affected neurological functions. CONCLUSION: This case highlights an unusual presentation of a rare disease leading to a delay in diagnosis and the importance of a complete workup for trigeminal neuropathy.


Assuntos
Linfoma/diagnóstico , Neoplasias da Língua/diagnóstico , Neuralgia do Trigêmeo/diagnóstico , Protocolos de Quimioterapia Combinada Antineoplásica , Biópsia , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Ciclofosfamida , Diagnóstico Diferencial , Doxorrubicina , Feminino , Humanos , Linfoma/tratamento farmacológico , Imagem por Ressonância Magnética , Mamografia , Pessoa de Meia-Idade , Neoplasias Primárias Múltiplas/diagnóstico por imagem , Neoplasias Primárias Múltiplas/tratamento farmacológico , Prednisona , Rituximab , Neoplasias da Língua/tratamento farmacológico , Vincristina
16.
Int J Mol Sci ; 20(15)2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31374832

RESUMO

Chronic inflammation can lead to tumour initiation and progression. Vitamin B complex has the ability to regulate the immune response and, therefore, inflammation but many of the mechanistic and molecular processes involved in this regulation are still not fully understood. This study sought to determine some of these processes by studying the effects of vitamin B2 (riboflavin) B6 (pyridoxine) and B9 (folic acid) on un-differentiated pro-monocytic lymphoma cells in regard to their ability to alter the proliferation, migration, apoptosis, cytokines and expression levels of programmed death ligand 1. We show that vitamin B2, B6 and B9, on pro-monocytic lymphoma cells exerted an anti-tumorigenic effect. This data could form the basis for future studies in using vitamin B supplementation to reduce cancer cell growth in vivo.


Assuntos
Anticarcinógenos/farmacologia , Ácido Fólico/farmacologia , Linfoma/tratamento farmacológico , Riboflavina/farmacologia , Vitamina B 6/farmacologia , Adulto , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Humanos , Linfoma/patologia , Masculino
17.
Vet Clin North Am Small Anim Pract ; 49(5): 781-791, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31280902

RESUMO

Molecular diagnostics have revolutionized human oncology to allow early detection, targeted therapy, monitoring throughout treatment, and evidence of recurrence. By identifying genetic signatures associated with cancers, liquid biopsy techniques have been developed to diagnose and monitor cancer in noninvasive or minimally invasive ways. These techniques offer new opportunities for improving cancer screening, diagnosis, and monitoring the impact of therapy on the patients over time. Liquid biopsy also drives drug development programs. Similar diagnostics hold promise for comparable results in the veterinary field. Several noninvasive/minimally invasive techniques have been described in veterinary medicine that could be referred to as liquid biopsy.


Assuntos
Doenças do Cão/diagnóstico , Biópsia Líquida/veterinária , Neoplasias/veterinária , Animais , Carcinoma de Células de Transição/diagnóstico , Carcinoma de Células de Transição/genética , Carcinoma de Células de Transição/veterinária , Doenças do Cão/tratamento farmacológico , Doenças do Cão/genética , Cães , Detecção Precoce de Câncer/métodos , Detecção Precoce de Câncer/veterinária , Feminino , Humanos , Leucemia/diagnóstico , Leucemia/veterinária , Biópsia Líquida/métodos , Linfoma/diagnóstico , Linfoma/tratamento farmacológico , Linfoma/veterinária , Masculino , Terapia de Alvo Molecular/veterinária , Mutação , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Neoplasias/genética , Neoplasias Uretrais/diagnóstico , Neoplasias Uretrais/genética , Neoplasias Uretrais/veterinária , Neoplasias da Bexiga Urinária/veterinária
18.
Oncol Rep ; 42(3): 1248-1256, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31322273

RESUMO

Ribavirin exhibits inhibitory effects on the epigenetic enzyme enhancer of zeste homolog 2 (EZH2), which participates in lymphomagenesis. Additionally, preclinical and clinical studies have demonstrated the anti­lymphoma activity of this drug. To further investigate the potential of ribavirin as an anticancer treatment for lymphoma, the tumor­suppressive effects of ribavirin were analyzed in lymphoma cell lines. The effects of ribavirin on the viability and clonogenicity of the B­cell lymphoma cell line Pfeiffer (EZH2­mutant), Toledo (EZH2 wild­type) and cutaneous T­cell lymphoma Hut78 cell line were assessed. Expression of EZH2 and trimethylation status of histone 3, lysine 27 trimethylated (H3K27m3) was also determined in response to ribavirin. The transcriptional effects of ribavirin on Hut78 cells were analyzed by microarray expression and the results were validated by reverse transcription­quantitative polymerase chain reaction, western blotting and knockout of signal transducer and activator of transcription 1 (STAT1). The results of the present study demonstrated that ribavirin suppressed the growth and clonogenicity of cells in a dose­dependent manner. Ribavirin did not affect the expression of EZH2 nor altered its activity as evaluated by H3K27 trimethylation status. Furthermore, the results of transcriptome analysis indicated that the majority of the canonical pathways affected by ribavirin were associated with the immune system, including 'antigen presentation', 'communication between innate and adaptive immune cells' and 'cross­talk between dendritic and natural killer cells'. The results of gene expression analysis were confirmed, by demonstrating at the RNA and protein levels, downregulation of stearoyl­CoA desaturase and upregulation of STAT1. Depletion of STAT1, which was proposed as a key regulator of the aforementioned pathways, exerted growth inhibitory effects almost to the same extent as ribavirin. In conclusion, ribavirin was proposed to exert growth inhibitory effects on lymphoma cell lines, particularly Hut78 cells, a cutaneous T­cell lymphoma cell line. Of note, these effects may depend on, at least in part, the activation of canonical immune pathways regulated by the key factors STAT1 and interferon­Î³. Our results provide insight into the anti­lymphoma potential of ribavirin; however, further investigations in preclinical and clinical studies are required to determine the effectiveness of ribavirin as a therapeutic agent for treating lymphoma.


Assuntos
Antivirais/farmacologia , Apoptose/efeitos dos fármacos , Biomarcadores Tumorais/genética , Proliferação de Células/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Linfoma/patologia , Ribavirina/farmacologia , Biomarcadores Tumorais/metabolismo , Metilação de DNA , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Epigenômica , Perfilação da Expressão Gênica , Humanos , Linfoma/tratamento farmacológico , Linfoma/genética , Linfoma/metabolismo , Células Tumorais Cultivadas
19.
Turk J Med Sci ; 49(4): 985-992, 2019 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-31293116

RESUMO

Background/aim: High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) has become the standard approach for patients with relapsed/refractory Hodgkin's lymphoma (HL) or non-Hodgkin's lymphoma (NHL). In this study, we report the outcome of the mitoxantrone-melphalan conditioning regimen for lymphoma. Materials and methods: The study group included 53 patients who were relapsed/refractory HL (n = 14) and NHL (n = 39) and received mitoxantrone and melphalan followed by ASCT. The transplant regimen consisted of mitoxantrone (60 mg/m2) and melphalan (180 mg/m2) followed by peripheral blood stem cell infusion (PBSC). Results: Prior to high-dose chemotherapy, 37.7% of the patients were in complete remission (CR) and 45.3% were in partial remission (PR), and 17% had stable or progressive disease. After high-dose chemotherapy and PBSC, 44 out of 51 patients achieved CR (86.2%). CR was achieved in 24 out of 33 patients (72.7%) who were transplanted in a marginally active phase of the disease. At a median followup of 25.4 months (1.8­131.3 months) after ASCT, 13 patients relapsed/ progressed and 8 patients died. The estimated 2-year overall survival (OS) was 81.9%, and event-free survival (EFS) was 59.3%. Conclusion: High-dose chemotherapy followed by ASCT is an effective conditioning regimen in relapsed/refractory lymphoma patients who are undergoing ASCT.


Assuntos
Antineoplásicos/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Linfoma , Melfalan/uso terapêutico , Mitoxantrona/uso terapêutico , Adolescente , Adulto , Idoso , Feminino , Humanos , Linfoma/tratamento farmacológico , Linfoma/epidemiologia , Linfoma/patologia , Linfoma/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Adulto Jovem
20.
J Surg Oncol ; 120(3): 431-437, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31187517

RESUMO

BACKGROUND AND OBJECTIVES: Primary colonic lymphoma (PCL) is rare, heterogeneous, and presents a therapeutic challenge for surgeons. Optimal treatment strategies are difficult to standardize, leading to variation in therapy. Our objective was to describe the patient characteristics, short-term outcomes, and five-year survival of patients undergoing nonpalliative surgery for PCL. METHODS: We performed a retrospective cohort analysis in the National Cancer Database. Included patients underwent surgery for PCL between 2004 to 2014. Patients with metastases and palliative operations were excluded. Univariate predictors of overall survival were analyzed using multivariable Cox proportional hazard analysis. RESULTS: We identified 2153 patients. Median patient age was 68. Diffuse large B-cell lymphoma accounted for 57% of tumors. 30- and 90-Day mortality were high (5.6% and 11.1%, respectively). Thirty-nine percent of patients received adjuvant chemotherapy. For patients surviving 90 days, 5-year survival was 71.8%. Chemotherapy improved survival (surgery+chemo, 75.4% vs surgery, 68.6%; P = .01). Adjuvant chemotherapy was associated with overall survival after controlling for age, comorbidity, and lymphoma subtype (HR 1.27; 95% CI, 1.07-1.51; P = .01). CONCLUSIONS: Patients undergoing surgery for PCL have high rates of margin positivity and high short-term mortality. Chemotherapy improves survival, but <50% receive it. These data suggest the opportunity for improvement of care in patients with PCL.


Assuntos
Neoplasias do Colo/mortalidade , Neoplasias do Colo/cirurgia , Linfoma/mortalidade , Linfoma/cirurgia , Idoso , Idoso de 80 Anos ou mais , Big Data , Quimioterapia Adjuvante , Estudos de Coortes , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Linfoma/tratamento farmacológico , Linfoma/patologia , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/patologia , Linfoma Difuso de Grandes Células B/cirurgia , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/mortalidade , Linfoma não Hodgkin/patologia , Linfoma não Hodgkin/cirurgia , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Radioterapia Adjuvante , Estudos Retrospectivos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA