Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 5 de 5
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Br J Cancer ; 126(1): 134-143, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34611308

RESUMO

BACKGROUND: We wished to examine treatment and outcome patterns in older diffuse large B-cell lymphoma (DLBCL) patients, with a focus on the effect of route-to-diagnosis to outcome. METHODS: Data were extracted from Public Health England's National Cancer Registration and Analysis Service between 2013 and 2015 included route-to-diagnosis, disease characteristics and survival for 9186 patients ≥65 years. Systemic Anti-Cancer Therapy data identified front-line regimens, cycles and doses. RESULTS: Route-to-diagnosis were emergency (34%), NHS urgent cancer pathway (rapid haemato-oncologist review <2 weeks), (29%) and standard GP referral (25%). The most common regimen was R-CHOP (n = 4392). 313 patients received R-miniCHOP (7% of R-CHOP). For all patients, 3-year overall survival (OS) for 65-79 years was 57% and for ≥80 years was 32%. Three-year OS for R-CHOP-treated patients diagnosed via emergency presentation was 54% (adjusted hazard ratio (HR) 1.63, p < 0.01) and 75% (adjusted HR 0.81, p < 0.01) on the NHS urgent cancer pathway (reference HR:1.00: GP referrals). 3-year OS was 54% for both R-miniCHOP and R-CHOP in ≥80 years. CONCLUSIONS: Our comprehensive population analysis is the first to show that the NHS urgent cancer pathway is associated with a superior survival after adjusting for multiple confounders. Equivalent survival for R-CHOP and R-mini-CHOP was demonstrated in those ≥80 years.


Assuntos
Assistência Ambulatorial/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bases de Dados Factuais/estatística & dados numéricos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Padrões de Prática Médica/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Inglaterra/epidemiologia , Humanos , Linfoma Difuso de Grandes Células B/epidemiologia , Linfoma Difuso de Grandes Células B/patologia , Prednisona/uso terapêutico , Estudos Retrospectivos , Rituximab/uso terapêutico , Taxa de Sobrevida , Vincristina/uso terapêutico
2.
Oncogene ; 27(31): 4293-304, 2008 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-18408754

RESUMO

Lethal 3 malignant brain tumor 1 (L3MBTL1), a homolog of the Drosophila polycomb tumor suppressor l(3)mbt, contains three tandem MBT repeats (3xMBT) that are critical for transcriptional repression. We recently reported that the 3xMBT repeats interact with mono- and dimethylated lysines in the amino termini of histones H4 and H1b to promote methylation-dependent chromatin compaction. Using a series of histone peptides, we now show that the recognition of mono- and dimethylated lysines in histones H3, H4 and H1.4 (but not their trimethylated or unmodified counterparts) by 3xMBT occurs in the context of a basic environment, requiring a conserved aspartic acid (D355) in the second MBT repeat. Despite the broad range of in vitro binding, the chromatin association of L3MBTL1 mirrors the progressive accumulation of H4K20 monomethylation during the cell cycle. Furthermore, transcriptional repression by L3MBTL1 is enhanced by the H4K20 monomethyltransferase PR-SET7 (to which it binds) but not SUV420H1 (an H4K20 trimethylase) or G9a (an H3K9 dimethylase) and knockdown of PR-SET7 decreases H4K20me1 levels and the chromatin association of L3MBTL1. Our studies identify the importance of H4K20 monomethylation and of PR-SET7 for L3MBTL1 function.


Assuntos
Regulação da Expressão Gênica , Histona-Lisina N-Metiltransferase/química , Histonas/química , Proteínas de Neoplasias/metabolismo , Transcrição Gênica , Sítios de Ligação , Ciclo Celular , Cromatina/química , Cromatina/metabolismo , Proteínas Cromossômicas não Histona , Humanos , Células K562 , Lisina/química , Metilação , Ligação Proteica , Proteínas Repressoras , Proteínas Supressoras de Tumor
3.
Bone Marrow Transplant ; 35(5): 441-7, 2005 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15640822

RESUMO

Multiple myeloma (MM) is an incurable hematologic malignancy for which autologous hematopoietic stem cell transplantation (HCT) is a standard therapy. The optimal method of stem cell mobilization is not defined. We evaluated intravenous melphalan (60 mg/m2), the most effective agent for MM, and G-CSF (10 microg/kg/day) for mobilization. End points were safety, adequacy of CD34+ collections, MM response, and contamination of stem cell components (SCC). In total, 32 patients were mobilized. There were no deaths or significant bleeding episodes; 14 patients (44%) required hospitalization for neutropenic fever. Median days of grade 3 or 4 neutropenia or thrombocytopenia were 7 (2-20) and 8 (3-17). Median mobilization days, CD34+ cells/kg and total leukaphereses were 16 (12-30), 12.1 million (2.6-52.8), and 2 (1-5) respectively. Four patients (12.5 %) failed to achieve the target of 4 million CD34+ cells/kg in five leukaphereses. Reduction in myeloma was seen in 11 patients (34%) with 3 (9%) achieving complete response; 15 (47%) maintained prior responses. Estimated MM contamination per SCC (N=48) was 0.0009% (range 0-0.1) and 0.21 x 10(4) cells per kg (range 0-41.2). Increased contamination was associated with increased patient age. This strategy for mobilization is feasible, frequently requires hospitalization and transfusion, and controls disease in most patients.


Assuntos
Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Mobilização de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas/métodos , Melfalan/administração & dosagem , Mieloma Múltiplo/terapia , Adulto , Fatores Etários , Idoso , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Leucaférese/métodos , Masculino , Melfalan/toxicidade , Pessoa de Meia-Idade , Mieloma Múltiplo/complicações , Células Neoplásicas Circulantes/efeitos dos fármacos , Neutropenia , Transplante Autólogo , Resultado do Tratamento
4.
Br J Haematol ; 124(3): 309-14, 2004 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-14717777

RESUMO

Systemic AL amyloidosis (AL) is a disorder in which light chains form fibrillar deposits, leading to organ dysfunction and death. Rarely, AL has been associated with non-Hodgkin's lymphoma (NHL), although this association has not been well characterized. We report a series of six patients with AL associated with NHL, primarily lymphoplasmacytic lymphoma. Organ involvement was variable, with frequent bulky lymphadenopathy and visceral cavity deposits, but no cardiac involvement. Positron emission tomography scans were negative. Bone marrow and lymph node biopsies showed a mixed population of CD20+ lymphoid and CD138+ plasma cells. Serum free light chains were elevated, and correlated with response to therapy. Immunoglobulin light chain variable region (Ig VL) germline gene use was typical for AL, reflecting previously observed correlations between germline gene use and organ tropism. Five patients received rituximab-based therapies with two responses. Two patients underwent autologous stem cell transplantation with one complete haematological response. Four patients survive at 10-132 months from diagnosis. AL with NHL has distinctive clinical features but employs the same Ig VL gene repertoire as AL with clonal plasma cell dyscrasias. Serial serum free light chain levels are useful for tracking response to therapy. Treatments aimed at both lymphoid and plasma cell components appear warranted.


Assuntos
Amiloidose/etiologia , Linfoma não Hodgkin/complicações , Idoso , Amiloidose/genética , Amiloidose/terapia , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Murinos , Antineoplásicos/uso terapêutico , Feminino , Genes de Imunoglobulinas , Humanos , Cadeias Leves de Imunoglobulina/análise , Região Variável de Imunoglobulina , Linfoma não Hodgkin/genética , Linfoma não Hodgkin/terapia , Masculino , Pessoa de Meia-Idade , Rituximab , Transplante de Células-Tronco , Tomografia Computadorizada de Emissão
5.
Blood ; 98(5): 1555-60, 2001 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-11520807

RESUMO

Activating point mutations in codons 12, 13, or 61 of the K-ras and N-ras genes have been reported to occur in up to 40% of patients with multiple myeloma at presentation. In a study of 34 presentation myeloma cases using a sensitive polymerase chain reaction-restriction fragment length polymorphism strategy on enriched tumor cell populations, the present study detected N-ras codon 61 mutation-positive cells in all patients. Quantitative plaque hybridization using allele-specific oligonucleotide probes showed that in the majority of patients, ras mutation-positive cells comprise only a subpopulation of the total malignant plasma cell compartment (range, 12%-100%). Using clonospecific point mutations in the 5' untranslated region of the BCL6 gene to quantitate clonal B cells in FACS-sorted bone marrow populations from 2 patients, the representation of ras mutation-positive cells was independent of immunophenotype. These observations imply that mutational activation of N-ras codon 61 is a mandatory event in the pathogenesis of multiple myeloma; such mutations provide a marker of intraclonal heterogeneity that may originate at an earlier ontologic stage than immunophenotypic diversification of the malignant B cell clone.


Assuntos
Códon/genética , DNA de Neoplasias/genética , Genes ras , Mieloma Múltiplo/genética , Mutação , Regiões 5' não Traduzidas/genética , Substituição de Aminoácidos , Separação Celular , Transformação Celular Neoplásica/genética , Células Clonais/química , Células Clonais/patologia , Análise Mutacional de DNA , Proteínas de Ligação a DNA/genética , Feminino , Citometria de Fluxo , Humanos , Imunofenotipagem , Masculino , Mieloma Múltiplo/patologia , Mutação de Sentido Incorreto , Células-Tronco Neoplásicas/química , Células-Tronco Neoplásicas/patologia , Mutação Puntual , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas c-bcl-6 , Fatores de Transcrição/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...