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1.
Medicine (Baltimore) ; 97(6): e9799, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29419676

RESUMO

RATIONALE: Primary gastrointestinal mantle cell lymphoma is rare, and histopathological examination and specific immunohistochemical staining are still the gold standard for diagnosis. Therefore, it is necessary to find a new way to improve positive biopsy rates. PATIENT CONCERNS: A 58-year-old man was admitted to our hospital with epigastric pain, abdominal distension, nausea, and melena. Endoscopy identified submucosal neoplasms and diffuse gastrointestinal tract involvement including the esophagus. DIAGNOSES: A false-negative diagnosis was first determined by ordinary endoscopy. However, a large tissue biopsy was subsequently performed using endoscopic mucosal resection based on endoscopic ultrasonography (EUS). Pathological examination of the biopsy specimens taken from the lesions of the duodenum and rectum revealed diffuse lymphocytic proliferation and obscure nodular and small cleaved cells with irregularly shaped nuclei. Immunohistochemistry showed that the cells were positive for CyclinD1, BCL-2, CD20, CD21, and CD5; however, they were negative for CD3, CD6, CD10, and CD43. INTERVENTIONS: The patient refused to receive further treatment. OUTCOMES: Mantle cell lymphoma was conclusively diagnosed. CONCLUSIONS: EUS has an important role in the diagnosis and management of gastrointestinal submucosal tumors. Performing a pathological biopsy including EUS may be useful for identifying the unknown nature of tumors of the digestive tract.


Assuntos
Neoplasias Gastrointestinais , Linfoma de Célula do Manto , Biópsia/métodos , Ciclina D1/análise , Diagnóstico Diferencial , Duodeno/patologia , Ressecção Endoscópica de Mucosa/métodos , Endossonografia/métodos , Neoplasias Gastrointestinais/diagnóstico , Neoplasias Gastrointestinais/patologia , Neoplasias Gastrointestinais/fisiopatologia , Humanos , Imuno-Histoquímica , Linfoma de Célula do Manto/diagnóstico , Linfoma de Célula do Manto/patologia , Linfoma de Célula do Manto/fisiopatologia , Masculino , Pessoa de Meia-Idade , Reto/patologia
2.
Retin Cases Brief Rep ; 12(1): 5-9, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-27529778

RESUMO

PURPOSE: To report the successful treatment of a 78-year-old woman with bilateral mantle cell lymphoma involving the optic nerves. Chemotherapy initially was administered in the form of intravitreal methotrexate (MTX) monotherapy and was subsequently combined with systemic ibrutinib. METHODS: Retrospective case report. The diagnosis of CD5-negative mantle cell lymphoma was confirmed via immunohistopathological analysis of an axillary lymph node. Serial ophthalmologic examinations in conjunction with fluorescein angiography, fundus photography, and spectral domain optical coherence tomography were used to assess the treatment response. RESULTS: Prompt improvement in optic nerve infiltration, no significant side effects, and excellent tolerability were noted after two weekly injections of unilateral intravitreal MTX monotherapy. Combined systemic treatment with ibrutinib and bilateral weekly MTX intravitreal injections then resulted in continued regression of optic nerve infiltration bilaterally as confirmed by serial fundus photography and optical coherence tomography. After eight additional bilateral weekly injections, a mild MTX-associated keratopathy developed, which resolved promptly with cessation of injections and administration of topical lubrication. Six weeks after MTX cessation, but with continued ibrutinib treatment, the optic nerves revealed near-complete resolution of the lymphomatous infiltration and the visual acuity improved. CONCLUSION: Intravitreal MTX injections and systemic ibrutinib may represent effective treatment options for patients diagnosed with intraocular mantle cell lymphoma.


Assuntos
Linfoma de Célula do Manto/tratamento farmacológico , Metotrexato/administração & dosagem , Neoplasias do Nervo Óptico/tratamento farmacológico , Nervo Óptico/patologia , Idoso , Antimetabólitos Antineoplásicos/administração & dosagem , Relação Dose-Resposta a Droga , Esquema de Medicação , Quimioterapia Combinada , Feminino , Angiofluoresceinografia/métodos , Seguimentos , Fundo de Olho , Humanos , Injeções Intravítreas , Linfoma de Célula do Manto/diagnóstico , Linfoma de Célula do Manto/fisiopatologia , Neoplasias do Nervo Óptico/diagnóstico , Neoplasias do Nervo Óptico/fisiopatologia , Pirazóis/administração & dosagem , Pirimidinas/administração & dosagem , Tomografia de Coerência Óptica/métodos , Acuidade Visual , Corpo Vítreo
3.
Med. clín (Ed. impr.) ; 147(1): 18-21, jul. 2016. graf
Artigo em Espanhol | IBECS | ID: ibc-153867

RESUMO

Fundamento y objetivo: El linfoma de células del manto (LCM) es un linfoma poco frecuente, con recaídas habituales y mal pronóstico. Este estudio analiza la respuesta al tratamiento y el pronóstico en una serie de pacientes con LCM. Pacientes y método: Estudio retrospectivo de los pacientes con LCM diagnosticados en un centro entre 1996 y 2013. Se dividió la cohorte en función del tratamiento recibido. Resultados: Se incluyeron 45 pacientes (32 varones) con una edad mediana de 66 años. Veintiún pacientes recibieron quimioterapia o quimioinmunoterapia intensiva (pautas con citarabina a dosis altas), 13 semiintensiva (sin citarabina a dosis altas), 8 no intensiva y 3 no precisaron tratamiento. La respuesta global fue del 85% con tratamiento intensivo y del 77% con semiintensivo. En el análisis multivariable el tratamiento intensivo se asoció a una mayor probabilidad de supervivencia libre de progresión (SLP) y supervivencia global (SG) (hazard ratio de 9,8 [IC 95% 2,7-35,5], p = 0,001 para la SLP y 4,5 [1,2-17,8], p = 0,03 para la SG). Conclusiones: En esta serie retrospectiva de pacientes con LCM el tratamiento intensivo se asoció a mejores resultados respecto al resto de las modalidades de tratamiento (AU)


Background and purpose Mantle cell lymphoma (MCL) is a rare lymphoproliferative disorder, with frequent relapses and a poor prognosis. This study analyzes response to treatment and prognosis in a series of MCL patients. Patients and method: Retrospective study of MCL patients diagnosed in a single institution between 1996 and 2013. The cohort was divided according to the treatment received. Results: Forty-five patients were included (32 male) with a median age of 66 years old. Twenty-one received intensive chemotherapy or chemoimmunotherapy (based on high-dose cytarabine), 13 semi-intensive (without high-dose cytarabine), 8 not intensive and 3 did not require treatment. Overall response rate was 85% in the intensive and 77% in the semi-intensive treatment groups. In multivariate analysis, intensive treatment was correlated with a longer progression-free survival (hazard ratio 9.8 [95% CI 2.7-35.5], P = .001) and overall survival (4.5 [1.2-17.8], P = .03). Conclusions: In this retrospective series of MCL patients, intensive treatment was correlated with better outcomes than the other treatment modalities (AU)


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Linfoma de Célula do Manto/diagnóstico , Linfoma de Célula do Manto/epidemiologia , Prognóstico , Citarabina/metabolismo , Citarabina/uso terapêutico , Dose Máxima Permissível/métodos , Ciclofosfamida/uso terapêutico , Prednisona/uso terapêutico , Linfoma de Célula do Manto/prevenção & controle , Linfoma de Célula do Manto/fisiopatologia , Linfoma de Célula do Manto/terapia , Relação Dose-Resposta a Droga , Estudos Retrospectivos , Doxorrubicina/uso terapêutico
4.
J Clin Apher ; 31(4): 398-402, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26332581

RESUMO

Mantle cell lymphoma is an aggressive malignant B-cell disorder that often presents with a leukemic picture. Circulating lymphoma cell morphology may vary from small round mature-appearing lymphocytes resembling the lymphocytes of chronic lymphocytic leukemia to large prolymphocytoid or blastoid cells. Rare reports of hyperleukocytosis with leukostasis, treated with leukocytapheresis, are described in patients with prolymphocytoid or blastoid morphology. We report an 88 year old woman with mantle cell lymphoma, hyperleukocytosis (WBC > 400 × 10(3) /µL) with severe respiratory compromise but without interstitial or alveolar infiltrates on radiograph or computerized tomography of the chest. She was afebrile and had no central nervous system signs. Circulating lymphoma cell morphology was predominantly of the small lymphocyte type. A two-whole-blood-volume leukocytapheresis reduced her WBC from 465 to 221 × 10(3) /µL in 150 min. Her respiratory rate decreased from 28/min to 18/min and her arterial oxygen saturation (SpO2 ) rose from 91% to 97% on 6 L/min of oxygen by nasal cannula. Severe breathlessness before the procedure abated completely by the end of the procedure. Respiratory compromise may occur in mantle cell lymphoma with hyperleukocytosis with a mature lymphoma cell phenotype, even without a clear picture of leukostasis. Although the ultimate survival of the patient depends on treatment with chemotherapy, leukocytapheresis for alleviation of symptoms may be warranted and should be considered. Respiratory status and response to leukocytapheresis should be documented with physiological measurements. J. Clin. Apheresis 31:398-402, 2016. © 2015 Wiley Periodicals, Inc.


Assuntos
Leucaférese/métodos , Leucocitose/terapia , Linfócitos/patologia , Linfoma de Célula do Manto/terapia , Idoso de 80 Anos ou mais , Tamanho Celular , Feminino , Humanos , Leucocitose/complicações , Leucocitose/fisiopatologia , Linfoma de Célula do Manto/complicações , Linfoma de Célula do Manto/fisiopatologia , Transtornos Respiratórios/etiologia , Transtornos Respiratórios/terapia
5.
Cancer Chemother Pharmacol ; 76(1): 211-6, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26006703

RESUMO

PURPOSE: Bendamustine is used in chronic lymphocytic leukemia (first-line) and indolent B-cell non-Hodgkin lymphoma (NHL) that progressed during/within 6 months of treatment with rituximab or a rituximab-containing regimen. This study was a postapproval commitment to investigate bendamustine's effect on cardiac repolarization in treatment-naïve adults with advanced indolent NHL/mantle cell lymphoma (MCL). METHODS: In this multicenter, open-label, phase 3 study, patients received 6-8 28-day cycles of bendamustine (90 mg/m(2), days 1 and 2) and rituximab (375 mg/m(2), day 1). Exclusions included a history of cardiac conditions with potential for QT prolongation. The primary endpoint was change in Fridericia-corrected QT (QTcF; 3 electrocardiograms per time point) on day 2 of cycle 1, from just before infusion to end of infusion (immediately postinfusion, coinciding with maximum plasma concentration of bendamustine). Change 1 h postinfusion was also measured. Exploratory assessments included specific QTcF outlier analyses (new QTcF >500 ms, change >60 ms) and morphological changes. RESULTS: Of the 54 enrolled patients (mean age, 62.9 years), 53 received ≥1 dose; 49 completed ≥6 cycles. Mean QTcF change from baseline was 6.7 ms at end of infusion; no mean changes >20 ms were detected ≤1 h postinfusion. No patients met specific outlier criteria at end of infusion or 1 h postinfusion. No morphological changes were detected. CONCLUSIONS: In this small treatment-naïve population with advanced NHL/MCL, bendamustine did not produce a clinically relevant increase in mean QTcF on the second infusion day. The potential for delayed effects on QT interval after 1 h was not evaluated.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Frequência Cardíaca/efeitos dos fármacos , Linfoma de Célula do Manto/tratamento farmacológico , Linfoma não Hodgkin/tratamento farmacológico , Anticorpos Monoclonais Murinos/administração & dosagem , Anticorpos Monoclonais Murinos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Cloridrato de Bendamustina , Eletrocardiografia/efeitos dos fármacos , Feminino , Humanos , Linfoma de Célula do Manto/fisiopatologia , Linfoma não Hodgkin/fisiopatologia , Masculino , Pessoa de Meia-Idade , Compostos de Mostarda Nitrogenada/administração & dosagem , Compostos de Mostarda Nitrogenada/farmacologia , Rituximab
6.
Cell Death Dis ; 5: e1013, 2014 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-24457957

RESUMO

Mantle cell lymphoma (MCL) is an aggressive lymphoid neoplasm with transient response to conventional chemotherapy. We here investigated the role of the Bcl-2 homology domain 3-only protein NOXA for life-death decision in MCL. Surprisingly, NOXA (PMAIP1) mRNA and NOXA protein levels were extremely discrepant in MCL cells: NOXA mRNA was found to be highly expressed whereas NOXA protein levels were low. Chronic active B-cell receptor signaling and to a minor degree cyclin D1 overexpression contributed to high NOXA mRNA expression levels in MCL cells. The phoshatidyl-inositol-3 kinase/AKT/mammalian target of rapamycin pathway was identified as the major downstream signaling pathway involved in the maintenance of NOXA gene expression. Interestingly, MCL cells adapt to this constitutive pro-apoptotic signal by extensive ubiquitination and rapid proteasomal degradation of NOXA protein (T½âˆ¼15-30 min). In addition to the proteasome inhibitor Bortezomib, we identified the neddylation inhibitor MLN4924 and the fatty acid synthase inhibitor Orlistat as potent inducers of NOXA protein expression leading to apoptosis in MCL. All inhibitors targeted NOXA protein turnover. In contrast to Bortezomib, MLN4924 and Orlistat interfered with the ubiquitination process of NOXA protein thereby offering new strategies to kill Bortezomib-resistant MCL cells. Our data, therefore, highlight a critical role of NOXA in the balance between life and death in MCL. The discrepancy between NOXA transcript and protein levels is essential for sensitivity of MCL to ubiquitin-proteasome system inhibitors and could therefore provide a druggable Achilles' heel of MCL cells.


Assuntos
Linfoma de Célula do Manto/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Apoptose , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Humanos , Linfoma de Célula do Manto/metabolismo , Linfoma de Célula do Manto/fisiopatologia , Fosfatidilinositol 3-Quinases/metabolismo , Estabilidade Proteica , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/química , Transdução de Sinais
7.
Proc Natl Acad Sci U S A ; 110(45): 18250-5, 2013 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-24145436

RESUMO

Mantle cell lymphoma (MCL) is an aggressive tumor, but a subset of patients may follow an indolent clinical course. To understand the mechanisms underlying this biological heterogeneity, we performed whole-genome and/or whole-exome sequencing on 29 MCL cases and their respective matched normal DNA, as well as 6 MCL cell lines. Recurrently mutated genes were investigated by targeted sequencing in an independent cohort of 172 MCL patients. We identified 25 significantly mutated genes, including known drivers such as ataxia-telangectasia mutated (ATM), cyclin D1 (CCND1), and the tumor suppressor TP53; mutated genes encoding the anti-apoptotic protein BIRC3 and Toll-like receptor 2 (TLR2); and the chromatin modifiers WHSC1, MLL2, and MEF2B. We also found NOTCH2 mutations as an alternative phenomenon to NOTCH1 mutations in aggressive tumors with a dismal prognosis. Analysis of two simultaneous or subsequent MCL samples by whole-genome/whole-exome (n = 8) or targeted (n = 19) sequencing revealed subclonal heterogeneity at diagnosis in samples from different topographic sites and modulation of the initial mutational profile at the progression of the disease. Some mutations were predominantly clonal or subclonal, indicating an early or late event in tumor evolution, respectively. Our study identifies molecular mechanisms contributing to MCL pathogenesis and offers potential targets for therapeutic intervention.


Assuntos
Evolução Clonal/genética , Variação Genética , Genoma Humano/genética , Linfoma de Célula do Manto/genética , Mutação/genética , Proteínas Mutadas de Ataxia Telangiectasia/genética , Sequência de Bases , Ciclina D1/genética , Estudo de Associação Genômica Ampla , Genômica/métodos , Genótipo , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Linfoma de Célula do Manto/fisiopatologia , Análise em Microsséries , Dados de Sequência Molecular , Receptor Notch2/genética , Receptor 2 Toll-Like/genética
8.
Blood ; 121(12): 2175-85, 2013 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-23321250

RESUMO

Mantle cell lymphoma (MCL) is one of the most aggressive lymphoid neoplasms whose pathogenesis is not fully understood. The neural transcription factor SOX11 is overexpressed in most MCL but is not detected in other mature B-cell lymphomas or normal lymphoid cells. The specific expression of SOX11 in MCL suggests that it may be an important element in the development of this tumor, but its potential function is not known. Here, we show that SOX11 promotes tumor growth in a MCL-xenotransplant mouse model. Using chromatin immunoprecipitation microarray analysis combined with gene expression profiling upon SOX11 knockdown, we identify target genes and transcriptional programs regulated by SOX11 including the block of mature B-cell differentiation, modulation of cell cycle, apoptosis, and stem cell development. PAX5 emerges as one of the major SOX11 direct targets. SOX11 silencing downregulates PAX5, induces BLIMP1 expression, and promotes the shift from a mature B cell into the initial plasmacytic differentiation phenotype in both primary tumor cells and an in vitro model. Our results suggest that SOX11 contributes to tumor development by altering the terminal B-cell differentiation program of MCL and provide perspectives that may have clinical implications in the diagnosis and design of new therapeutic strategies.


Assuntos
Linfócitos B/fisiologia , Diferenciação Celular/genética , Linfoma de Célula do Manto/genética , Fator de Transcrição PAX5/genética , Fatores de Transcrição SOXC/fisiologia , Animais , Linfócitos B/metabolismo , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Células HEK293 , Humanos , Linfoma de Célula do Manto/patologia , Linfoma de Célula do Manto/fisiopatologia , Linfopoese/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos SCID , Invasividade Neoplásica , Fator de Transcrição PAX5/metabolismo , Fatores de Transcrição SOXC/genética , Fatores de Transcrição SOXC/metabolismo , Transplante Heterólogo
9.
Autophagy ; 9(1): 115-7, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23079699

RESUMO

Mantle cell lymphoma (MCL) is an aggressive neoplasm, which lacks effective therapy. The mechanistic target of rapamycin (MTOR) kinase inhibitor everolimus (RAD001) has shown activity in preclinical and clinical models of MCL, despite the fact that its mechanism of action has not been fully elucidated. We found that everolimus activity in MCL cells is closely linked to AKT phosphorylation status, and that the prevention of AKT rephosphorylation upon everolimus treatment by means of a selective AKT inhibitor, greatly enhances everolimus activity. Furthermore, our data show that an accumulation of autophagic vacuoles correlates with a lack of efficacy of dual AKT-MTOR targeting and that the complete therapeutic potential of this strategy can be restored by ATG gene selective knockdown or secondary inhibition of autolysosome formation by hydroxychloroquine. We thus demonstrated for the first time that the use of an autophagy inhibitor can overcome resistance to the combination of MTOR and AKT inhibitors in MCL cell lines and primary samples, demonstrating the prosurvival role of autophagy in AKT-MTOR compromised cells, and pointing out some potential opportunities using this triple combinational strategy in hematological malignancies.


Assuntos
Autofagia/fisiologia , Linfoma de Célula do Manto/tratamento farmacológico , Linfoma de Célula do Manto/patologia , Sirolimo/análogos & derivados , Antineoplásicos/farmacologia , Autofagia/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos , Everolimo , Humanos , Linfoma de Célula do Manto/fisiopatologia , Modelos Biológicos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Sirolimo/farmacologia , Serina-Treonina Quinases TOR/metabolismo , Células Tumorais Cultivadas
10.
Expert Opin Drug Metab Toxicol ; 8(11): 1455-68, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22970741

RESUMO

INTRODUCTION: Bendamustine , a cytotoxic agent comprising structural features of both an alkylating drug and a purine nucleoside analog, was approved by the US FDA for treatment of chronic lymphocytic leukemia (CLL) and indolent B-cell non-Hodgkin's lymphoma (NHL). Additionally, in Europe the drug has been also approved for treatment of multiple myeloma (MM) and in Asia, especially in Japan for refractory/relapsed NHL and mantle cell lymphoma. AREAS COVERED: The authors present the chemical structure, mechanism of action, pharmacokinetic properties and clinical application of bendamustine in hematological malignancies. Publications in English related to the above, up to June 2012, have been surveyed in the MEDLINE database. Conference proceedings reports from the last 5 years are also included. Additional relevant publications have been obtained by reviewing the references from the chosen articles. EXPERT OPINION: The availability of bendamustine provides an effective treatment option for patients with lymphoid malignancies. Several recent clinical trials have documented the activity of bendamustine in CLL, NHL and MM, both as a single agent and in combination with other cytotoxic drugs. However, doses, schedules and also the role of bendamustine in treatment of patients with hematological malignancies should be further investigated to establish its real place in the management of these diseases.


Assuntos
Antineoplásicos/farmacologia , Antineoplásicos/farmacocinética , Linfócitos B/efeitos dos fármacos , Linfoma de Células B/tratamento farmacológico , Compostos de Mostarda Nitrogenada/farmacologia , Compostos de Mostarda Nitrogenada/farmacocinética , Administração Intravenosa , Linfócitos B/patologia , Cloridrato de Bendamustina , Avaliação de Medicamentos , Europa (Continente) , Humanos , Japão , Linfoma de Células B/fisiopatologia , Linfoma de Célula do Manto/tratamento farmacológico , Linfoma de Célula do Manto/fisiopatologia , Compostos de Mostarda Nitrogenada/química , Estados Unidos
11.
Am J Hematol ; 87(8): 754-9, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22641457

RESUMO

Prior studies describe an increased incidence of lymphoma in celiac disease. However, few studies differentiate among lymphoproliferative disorders (LPDs). Our aim was to determine incidences of LPD subtypes in celiac disease patients, describe patterns of celiac disease presentation in patients who develop LPD, and compare survival in patients with various LPD subtypes. We conducted a retrospective cohort study of adults with biopsy-proven celiac disease seen at a US referral center from 1981 to 2010, identified patients with comorbid LPD, and calculated standardized incidence ratios (SIR) for each LPD subtype. In our cohort of 1,285 patients with celiac disease, there were 40 patients with LPD [SIR = 6.48, 95% confidence interval (CI) = 4.62-8.64] including 33 with non-Hodgkin lymphoma (NHL, SIR = 6.91, 95% CI = 4.26-8.28). The incidences of NHL subtypes including enteropathy-associated T-cell (EATL, n = 12), non-EATL T-cell (SIR = 22.43, 95% CI = 7.08-46.41), diffuse large B-cell (SIR = 5.37, 95% CI = 1.93-10.52), mantle cell (SIR = 32.21, 95% CI = 6.07-78.97), and marginal zone (SIR = 37.17, 11.73-76.89) lymphoma remained significantly elevated when only those diagnosed with celiac before LPD were considered (n = 24, NHL SIR = 4.47, 95% CI = 2.86-6.44). Patients who developed LPD were older at time of celiac disease diagnosis (57.9 ± 15.5 versus 42.5 ± 17.4 years, P < 0.0001) and more likely to present with diarrhea (60.0% versus 39.8% P = 0.016), abdominal pain (17.5% versus 5.5% P = 0.0046), and/or weight loss (12.5% versus 4.0%, P = 0.028). EATL patients had a shorter average survival than non-EATL NHL patients (3.2 versus 15.0 years, P = 0.016). The incidence of LPD is increased in celiac disease patients. Those diagnosed later in life who present with symptoms of malabsorption are more likely to be diagnosed with LPD.


Assuntos
Doença Celíaca/mortalidade , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma de Célula do Manto/mortalidade , Linfoma não Hodgkin/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença Celíaca/diagnóstico , Doença Celíaca/fisiopatologia , Feminino , Humanos , Incidência , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/fisiopatologia , Linfoma de Célula do Manto/diagnóstico , Linfoma de Célula do Manto/fisiopatologia , Linfoma não Hodgkin/diagnóstico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
15.
Rev. argent. coloproctología ; 21(1): 18-23, jan.-mar. 2010. ilus
Artigo em Espanhol | LILACS | ID: lil-605352

RESUMO

Antecedentes: Los linfomas gastrointestinales agrupan diferentes lesiones y son objeto de permanente revisión. Se los considera de acuerdo a su histología y el estadio evolutivo, hechos que suelen guardar estrecha relación con la clínica, las conductas terapéuticas y el pronóstico. El tubo digestivo está afectado entre un 5 a 15 por ciento en los pacientes que padecen Linfoma no Hodking. El colon y recto son los sitios de menor frecuencia. Representa entre 0,2 a 0,6 por ciento de los tumores malignos colorrectales. El linfoma de células del manto es un subtipo de linfoma de células B, con una frecuencia del 5 al 10 por ciento dentro de los linfomas no Hodking. Objetivo: Presentar el caso de una manifestación colorrectal de linfoma de células del manto, sus características fisiopatológicas y sus alternativas terapéuticas. Pacientes y método: Paciente de 82 años consultó por proctorragia, diarrea crónica, pérdida de peso y mucorrea de más de tres meses de evolución. Se realizó videocolonoscopía constatándose a 10 cm del margen anal lesión mamelonada, friable, ulcerovegetante, extendida hasta sigma con múltiples pólipos sesiles y subpediculados de gran tamaño en cantidad mayor de 100, extendidos en todo el colon. El hallazgo en correlación con la clínica y la endoscopia es compatible con linfoma de células del manto en su forma de afectación extranodal gastrointestinal, y poliposis linfomatosa múltiple. Resultados: Se realizó seis esquemas de quimioterapia bajo la modalidad CHOOP (ciclofosfamida, doxirrubicina, vincristina, prednisona) conjuntamente la aplicación al comienzo de los ciclos con Rituximab (Anticuerpo monoclonal). Se realizó un control endoscópico y tomográfico demostrando remisión completa del compromiso colorrectal, ganglios mesentéricos y retroperitoneales. Se observó persistencia de masas mediastinicas intercavo-aorticas derrame pleural bilateral y dilatación cardiaca...


Background: Gastrointestinal Lymphomas different injuries and are grouped under constant review. They are considered according to their histology and stage of development, events that are closely related to the clinic, the therapeutic behavior and prognosis. The gastrointestinal tract is affected between 5 to 15 per cent in patients with non-Hodgkin lymphoma. The colon and rectum are less frequent sites. It represents between 0.2 and 0.6 per cent of malignant colorectal tumors. The mantle cell lymphoma is a subtype of B-cell lymphoma, with a frequency of 5 to 10 per cent in non-Hodgkin lymphoma. Objective: To present the case of a manifestation colorectal mantle cell lymphoma, pathophysiological characteristics and treatment options. Patients and methods: Patient 82 years consulting with bloody diarrhea, chronic diarrhea, weight loss and mucorrea more than three months of evolution. A colonoscopy was performed, confirmed a 10 cm from the anal injury swellings, extended to multi-sigma subpediculados sessile polyps and large in quantity greater than 100, spread throughout the colon. The finding in correlation with clinical and endoscopy is compatible with mantle cell lymphoma, as extranodal gastrointestinal involvement and multiple lymphomatous polyposis. Results: we performed six schemes in the form CHOOP chemotherapy (cyclophosphamide, doxirrubicina, vincristine, prednisone) combined the application at the beginning of the cycles with Rituximab (monoclonal antibody). We undertook a endoscopy and CT demonstrated complete remission of colorectal disease, commitment, mesenteric and retroperitoneal lymph nodes. Showed persistence of mediastinal masses, bilateral pleural effusion and cardiac dilatation. Today is free from colorectal disease and active monitoring by their serial mediastinal and their heart failure...


Assuntos
Humanos , Idoso de 80 Anos ou mais , Linfoma de Célula do Manto/fisiopatologia , Linfoma de Célula do Manto/patologia , Linfoma de Célula do Manto/tratamento farmacológico , Linfoma de Célula do Manto/terapia , Biópsia , Colonoscopia/métodos , Diagnóstico por Imagem , Quimioterapia Combinada , Neoplasias Gastrointestinais , Neoplasias Colorretais/fisiopatologia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/terapia , Tomografia Computadorizada por Raios X
16.
Leuk Res ; 33(11): 1437-9, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19523686

RESUMO

Mantle cell lymphoma (MCL) is an aggressive B cell malignancy, which is believed to originate from naïve B cells in the mantle zone of lymph nodes. We speculate that a possible mechanistic hypothesis for the generation of MCL is one in which receptor editing and germinal centre exclusion could be involved in the molecular development and in the display of clinical characteristics of this rare, aggressive and scarcely understood lymphoma. The hypothesis is supported by a preferential autoimmune related IGVH gene utilization in MCL, where VH3-21, VH4-34 and VH5-51 genes are predominant, and by the fact that MCL expresses immunoglobulin light chain (IgL) lambda more frequently than other non-Hodgkin's lymphomas and that IgL lambda-producing B cells usually delete one or both their IgL kappa genes.


Assuntos
Linfoma de Célula do Manto/fisiopatologia , Receptores de Superfície Celular/fisiologia , Autoimunidade , Centro Germinativo/fisiologia , Humanos
17.
Mol Cell Proteomics ; 8(7): 1501-15, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19346216

RESUMO

We used shotgun proteomics to identify plasma membrane and lipid raft proteins purified from B cells obtained from mantle cell lymphoma (MCL) patients in leukemic phase. Bioinformatics identified 111 transmembrane proteins, some of which were profiled in primary MCL cases, MCL-derived cell lines, and normal B cells using RT-PCR and Western blotting. Several transmembrane proteins, including CD27, CD70, and CD31 (PECAM-1), were overexpressed when compared with normal B cells. CD70 was up-regulated (>10-fold) in three of five MCL patients along with its cognate receptor CD27, which was up-regulated (4-9-fold) in five of five patients, suggesting that MCL cells may undergo autocrine stimulation via this signaling pathway. Activated calpain I and protein kinase C betaII were also detected in the plasma membranes, suggesting that these proteins are constitutively active in MCL. Protein kinase C betaII has been associated with lipid rafts, and shotgun proteomics/protein profiling revealed that key lipid raft proteins, raftlin (four of five patients) and CSK (C-terminal Src kinase)-binding protein (Cbp)/phosphoprotein associated with glycosphingolipid-enriched microdomains (PAG) (four of four patients) were down-regulated in MCL. Levels of other known lipid raft proteins, such as Lyn kinase and flotillin 1, were similar to normal B cells. However, 5-lipoxygenase (5-LO), a key enzyme in leukotriene biosynthesis, was associated with lipid rafts and was up-regulated approximately 7-fold in MCL compared with normal B cells. Significantly inhibitors of 5-LO activity (AA861) and 5-LO-activating protein (FLAP) (MK886, its activating enzyme) induced apoptosis in MCL cell lines and primary chronic lymphocytic leukemia cells, indicating an important role for the leukotriene biosynthetic pathway in MCL and other B cell malignancies. Thus, using shotgun proteomics and mRNA and protein expression profiling we identified a subset of known and unknown transmembrane proteins with aberrant expression in MCL plasma membranes. These proteins may play a role in the pathology of the disease and are potential therapeutic targets in MCL.


Assuntos
Membrana Celular/química , Linfoma de Célula do Manto/química , Linfoma de Célula do Manto/fisiopatologia , Proteínas de Membrana/análise , Proteínas de Neoplasias/análise , Análise Serial de Proteínas/métodos , Transdução de Sinais/fisiologia , Adulto , Animais , Apoptose/fisiologia , Araquidonato 5-Lipoxigenase/metabolismo , Membrana Celular/metabolismo , Biologia Computacional , Humanos , Isoenzimas/análise , Inibidores de Lipoxigenase , Masculino , Microdomínios da Membrana/química , Proteína Quinase C/análise , Proteína Quinase C beta , Proteômica/métodos , Células Tumorais Cultivadas
19.
Med Oncol ; 26(1): 45-8, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-18543133

RESUMO

Rituximab is a chimeric monoclonal antibody directed against the phosphoprotein CD20. Because of its efficacy and acceptable toxicity profile, rituximab is now commonly used for the treatment of CD20-positive B-cell malignancies, including B-cell non-Hodgkin's lymphoma. However, rituximab-induced acute thrombocytopenia is an extremely rare side effect. We report a case of acute thrombocytopenia occurring immediately after rituximab infusion in a mantle cell lymphoma patient with bone marrow involvement and massive splenomegaly. Although the mechanism of thrombocytopenia is still unclear, it is possible that tumor burden, bone marrow involvement, the presence of infusion-related symptoms, and mantle cell histology are related to this rare complication of rituximab therapy. Hence, rituximab should be used with caution in patients who have these factors, and clinicians must be aware of this rare, but serious, side effect.


Assuntos
Anticorpos Monoclonais/efeitos adversos , Linfoma de Célula do Manto/tratamento farmacológico , Trombocitopenia/induzido quimicamente , Doença Aguda , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Murinos , Antimetabólitos Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Exame de Medula Óssea , Ciclofosfamida/administração & dosagem , Citarabina/administração & dosagem , Dexametasona/administração & dosagem , Doxorrubicina/administração & dosagem , Humanos , Imunofenotipagem , Infusões Parenterais , L-Lactato Desidrogenase/sangue , Linfoma de Célula do Manto/sangue , Linfoma de Célula do Manto/patologia , Linfoma de Célula do Manto/fisiopatologia , Masculino , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Contagem de Plaquetas , Rituximab , Esplenomegalia , Trombocitopenia/sangue , Trombocitopenia/fisiopatologia , Vincristina/administração & dosagem
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