RESUMO
The eukaryotic initiation factor eIF4E is essential for cap-dependent initiation of translation in eukaryotes. Abnormal regulation of eIF4E has been implicated in oncogenic transformation. We developed an eIF4E-binding peptide derived from Angel1, a partner of eIF4E that we recently identified. We show here that this peptide fused to a penetratin motif causes drastic and rapid cell death in several epithelial cancer cell lines. This necrotic cell death was characterized by a drop in ATP levels with F-actin network injury being a key step in extensive plasma membrane blebbing and membrane permeabilization. This synthetic eIF4E-binding peptide provides a candidate pharmacophore for a promising new cancer therapy strategy.
Assuntos
Fator de Iniciação 4E em Eucariotos/metabolismo , Neoplasias/patologia , Peptídeos/farmacologia , Actinas/metabolismo , Animais , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Permeabilidade da Membrana Celular/efeitos dos fármacos , Estruturas da Membrana Celular/efeitos dos fármacos , Estruturas da Membrana Celular/metabolismo , Humanos , Necrose , Ligação Proteica/efeitos dos fármacos , Biossíntese de Proteínas/efeitos dos fármacos , Estabilidade Proteica/efeitos dos fármacos , CoelhosAssuntos
Neoplasias do Sistema Nervoso Central/patologia , Linfoma/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Nervoso Central/terapia , Quimioterapia Adjuvante , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos , Humanos , Linfoma/terapia , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Transplante de Células-Tronco , Resultado do TratamentoAssuntos
Cromossomos Humanos Par 1 , Cromossomos Humanos Par 9 , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/fisiologia , Leucemia de Células B/genética , Proteínas de Fusão Oncogênica/química , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Proteínas Proto-Oncogênicas c-abl/genética , Translocação Genética , Humanos , MasculinoAssuntos
Anticorpos Monoclonais Murinos/uso terapêutico , Coagulantes/efeitos adversos , Fator VIIa/efeitos adversos , Deficiência do Fator XIII/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Trombose/tratamento farmacológico , Idoso , Inibidores dos Fatores de Coagulação Sanguínea/sangue , Feminino , Humanos , Proteínas Recombinantes/efeitos adversos , Rituximab , Trombose/induzido quimicamente , Resultado do TratamentoAssuntos
Medicamentos Biossimilares/administração & dosagem , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Linfoma/terapia , Mieloma Múltiplo/terapia , Transplante de Células-Tronco de Sangue Periférico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosAssuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Talidomida/análogos & derivados , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Cisplatino/administração & dosagem , Citarabina/administração & dosagem , Etoposídeo/administração & dosagem , Transplante de Células-Tronco Hematopoéticas , Doença de Hodgkin/terapia , Humanos , Lenalidomida , Prednisona/administração & dosagem , Recidiva , Indução de Remissão , Talidomida/administração & dosagem , Transplante AutólogoRESUMO
Hodgkin's lymphoma is a disease with a high rate of curability under classic chemo-radiotherapy regimes. Complications due to chemotherapy could include viral reactivation due to chronic lymphopenia. BK virus (BKV) is a polyoma virus belonging to the Papovaviridae family with antibody seroprevalences in healthy populations varying from 60% to 80%. Initial infections are asymptomatic usually occur in early childhood, after which the viruses remain latent in the kidneys or urothelium. Reactivation of BKV occurs in individuals with severe immunosuppression during HIV infections, transplantation or, exceptionally, after classical chemotherapy. BKV incidence is approximately 0% to 5% in immunocompetent individuals. Reactivation is associated with nephropathy and haemorrhagic cystitis. Herein, we present a case of a haemorrhagic cystitis due to BKV reactivation in a patient with Hodgkin's disease treated with chemotherapy.
RESUMO
The factor H (FH) protein (also known as beta1H globulin) is the main regulator of the complement alternative pathway. It exhibits multivalent binding sites to the complement component C3b, and polyanions and one binding site to sialic acid and cell surfaces. These multiple binding sites confer to FH a decay-accelerating factor activity in the fluid phase as well as at the cell surface. A defect in FH activity or a FH protein deficiency triggers chronic inflammation and tissue injury, leading to various disorders impacting the kidney or the eye. In contrast, some pathogens, as well as cancer cells, develop various strategies to bind FH and thereby subvert a complement attack. We focus on the functions of FH, and review the main pathological conditions in which FH is involved. Since the pathogenesis is elusive, appropriate FH dosage in biological fluids and FH gene analysis may help in improving understanding of such diseases.
Assuntos
Fator H do Complemento/fisiologia , Animais , Artrite Reumatoide/imunologia , Ativação do Complemento , Fator H do Complemento/análise , Fator H do Complemento/genética , Humanos , Infecções/imunologia , Inflamação/imunologia , Nefropatias/imunologia , Neoplasias/imunologiaAssuntos
Ácidos Borônicos/uso terapêutico , Dexametasona/uso terapêutico , Células-Tronco Hematopoéticas , Leucaférese/métodos , Mieloma Múltiplo/terapia , Pirazinas/uso terapêutico , Transplante de Células-Tronco , Bortezomib , Quimioterapia Combinada , Mobilização de Células-Tronco Hematopoéticas , Humanos , Transplante AutólogoAssuntos
Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/efeitos adversos , Síndromes Mielodisplásicas/tratamento farmacológico , Talidomida/administração & dosagem , Talidomida/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
We report a case of microsporidiosis in a 72-year-old woman presenting with prolymphocytic leukemia. The underlying conditions 7 months after leukemia was diagnosed were pancytopenia and immunosuppression due to alemtuzumab and pentostatin. The patient's status had worsened and she presented with dysuria. Urine cultures for bacteria were repeatedly negative. She was first empirically treated with broad-spectrum antibiotics. Three months later, urinary symptoms were persisting. Her blood lymphocyte count was 90/microl. Urine examination was positive for microsporidia using modified trichrome staining and Uvitex 2B fluorescence. Microsporidia were also detected in stools. The patient was cured by albendazole. This was consistent with an infection due to Encephalitozoon sp. Concurrently, disseminated toxoplasmosis was diagnosed. Toxoplasma gondii was detected in bone marrow, broncho-alveolar lavage and cerebrospinal fluid. She was successfully treated with sulfadiazine-pyrimethamine. Four cases of microsporidiosis in myeloid leukemic patients have been already described. The present case in a patient with lymphoid leukemia is the first to be reported.
Assuntos
Encefalitozoonose/complicações , Leucemia Prolinfocítica de Células T/complicações , Idoso , Albendazol/uso terapêutico , Animais , Medula Óssea/parasitologia , Encephalitozoon/isolamento & purificação , Encefalitozoonose/tratamento farmacológico , Fezes/microbiologia , Feminino , Humanos , Leucemia Prolinfocítica de Células T/microbiologia , Toxoplasma/isolamento & purificação , Toxoplasmose/complicações , Toxoplasmose/tratamento farmacológicoRESUMO
OBJECTIVES: Investigating the relationship between occupational exposure to pesticides and the risk of lymphoid neoplasms (LNs) in men. METHODS: A hospital-based case-control study was conducted in six centres in France between 2000 and 2004. The cases were incident cases with a diagnosis of LN aged 18-75 years. During the same period, controls of the same age and sex as the cases were recruited in the same hospital, mainly in the orthopaedic and rheumatological departments. Exposures to pesticides were evaluated through specific interviews and case-by-case expert reviews. Four hundred and ninety-one cases (244 cases of non-Hodgkin's lymphoma (NHL), 87 of Hodgkin's lymphoma (HL), 104 of lymphoproliferative syndromes (LPSs) and 56 of multiple myeloma (MM) cases) and 456 controls were included in the analyses. The odds ratios (ORs) and 95% CI were estimated using unconditional logistic regressions. RESULTS: Positive associations between HL and occupational exposure to triazole fungicides and urea herbicides were observed (OR = 8.4 (2.2 to 32.4), 10.8 (2.4 to 48.1), respectively). Exposure to insecticides, fungicides and herbicides were linked to a threefold increase in MM risk (OR = 2.8 (1.2 to 6.5), 3.2 (1.4 to 7.2), 2.9 (1.3 to 6.5)). For LPS subtypes, associations restricted to hairy-cell leukaemia (HCL) were evidenced for exposure to organochlorine insecticides, phenoxy herbicides and triazine herbicides (OR = 4.9 (1.1 to 21.2), 4.1 (1.1 to 15.5), 5.1 (1.4 to 19.3)), although based on small numbers. Lastly, despite the increased ORs for organochlorine and organophosphate insecticides, carbamate fungicides and triazine herbicides, no significant associations were evidenced for NHL. CONCLUSIONS: The results, based on case-by-case expert review of occupation-specific questionnaires, support the hypothesis that occupational pesticide exposures may be involved in HL, MM and HCL and do not rule out a role in NHL. The analyses identified specific pesticides that deserve further investigation and the findings were consistent with those of previous studies.
Assuntos
Leucemia de Células Pilosas/epidemiologia , Linfoma/epidemiologia , Doenças Profissionais/epidemiologia , Exposição Ocupacional/estatística & dados numéricos , Praguicidas/toxicidade , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Emprego/estatística & dados numéricos , França/epidemiologia , Fungicidas Industriais/toxicidade , Herbicidas/toxicidade , Doença de Hodgkin/induzido quimicamente , Doença de Hodgkin/epidemiologia , Humanos , Inseticidas/toxicidade , Leucemia de Células Pilosas/induzido quimicamente , Linfoma/induzido quimicamente , Linfoma não Hodgkin/induzido quimicamente , Linfoma não Hodgkin/epidemiologia , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/induzido quimicamente , Mieloma Múltiplo/epidemiologia , Doenças Profissionais/induzido quimicamente , Exposição Ocupacional/efeitos adversos , Adulto JovemRESUMO
OBJECTIVE: To study potential role of smoking and alcohol in lymphoid neoplasms (LN). METHODS: A case-control study that included 824 cases and 752 hospital controls aged 18-75 years was conducted. Cases were newly diagnosed with non-Hodgkin's or Hodgkin's lymphoma, multiple myeloma, or lymphoproliferative syndrome (LPS). Controls were matched with the cases by gender, age, and center. RESULTS: Overall, smoking was not related to LN. However, average tobacco consumption tended to be inversely related to non-Hodgkin's lymphoma (NHL), LPS, and the hairy cell leukemia (HCL) subtype, with a significant negative trend for the latter (OR of 0.4, 0.2, 0.1 for consumptions of
Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Doença de Hodgkin/epidemiologia , Linfoma não Hodgkin/epidemiologia , Mieloma Múltiplo/epidemiologia , Fumar/efeitos adversos , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Feminino , França/epidemiologia , Hospitais/estatística & dados numéricos , Humanos , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco , Fatores Socioeconômicos , Adulto JovemRESUMO
BACKGROUND: Congenital cutaneous leukaemia is rare. PATIENTS AND METHODS: A two-month-old girl presented bluish cutaneous macules of the trunk, histological examination of which suggested acute myeloid leukaemia (LAM B 5). The blood picture was negative for circulating tumour cells and the outcome under chemotherapy was favourable at one year of follow-up. DISCUSSION: The prognosis of congenital leukaemia is serious. Aleukaemic congenital leukaemia is seen occasionally but is rare. The existence of multiple cutaneous tumours in newborn infants raises the possibility of TORCH infection and of other malignant tumours such as nephroblastoma or neuroblastoma.
Assuntos
Leucemia Mieloide/patologia , Infiltração Leucêmica , Pele/patologia , Feminino , Humanos , LactenteRESUMO
OBJECTIVES: Investigating the relationship between skin type, UV exposure, and lymphoid malignancies (LM). METHODS: We conducted a hospital-based case-control study in France, including 813 incident cases of non-Hodgkin's lymphoma (NHL), Hodgkin's lymphoma (HL), lymphoproliferative syndrome (LPS) or multiple myeloma and 748 controls. RESULTS: Positive associations between HL and blond/red hair (OR = 1.8 [0.8-3.8]), very fair/fair skin (OR = 1.6 [1.0-2.5]) were observed. High propensity to burn was associated with HL (OR = 1.5 [1.0-2.2]) and LPS (OR = 1.4 [1.0-2.1]). Poor ability to tan was significantly associated with HL (OR = 1.7 [1.0-2.8]). Having light hair with high propensity to burn was associated with NHL (OR = 1.5 [0.9-2.5]) and significantly with HL (OR = 3.4 [1.4-8.4]). Having dark hair with high propensity to burn was significantly associated with LPS (OR = 1.5 [1.0-2.2]). The associations with HL and NHL were significant for men only, with significant interactions. Outdoors activities since leaving school or in the last decade were not related to LM. Only an almost negative trend was observed. Prior exposure to artificial UV was not associated with LM. CONCLUSION: These results suggest a positive association between the most reactive and palest skin types and NHL or HL in men and do not rule out a slight negative relationship between UV exposure and LM.
Assuntos
Transtornos Linfoproliferativos/etiologia , Pigmentação da Pele , Raios Ultravioleta/efeitos adversos , Adulto , Idoso , Estudos de Casos e Controles , Cor de Olho , Feminino , França , Cor de Cabelo , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
One hundred de novo multiple myeloma patients with t(4;14) treated with double intensive therapy according to IFM99 protocols were retrospectively analyzed. The median overall survival (OS) and event-free survival (EFS) were 41.4 and 21 months, respectively, as compared to 65 and 37 for patients included in the IFM99 trials without t(4;14) (P<10(-7)). We identified a subgroup of patients presenting at diagnosis with both low beta(2)-microglobulin <4 mg/l and high hemoglobin (Hb) >/=10 g/l (46% of the cases) with a median OS of 54.6 months and a median EFS of 26 months, respectively, which benefits from high-dose therapy (HDT); conversely patients with one or both adverse prognostic factor (high beta(2)-microglobulin and/or low Hb) had a poor outcome. The achievement of either complete response or very good partial response after HDT was also a powerful independent prognostic factor for both OS and EFS.