RESUMO
BACKGROUND: Pretransplantation soluble CD30 (sCD30) has been shown to be a good predictor of acute rejection (AR) and graft loss. This study aimed to evaluate the effectiveness of sCD30 measured pretransplant and up to 6 months after transplantation as a predictor of AR, graft loss, and survival at 5 years post-transplantation. Subjects were patients receiving living donor renal transplants at Bonsucesso Federal Hospital (Rio de Janeiro) in 2006 and between August 2010 and May 2011. METHODS: sCD30 was analyzed in samples collected pretransplantation and 7, 14, and 21, 28 days and 3, 4, 5, and 6 months post-transplantation from 73 kidney recipients. RESULTS: Patients in the AR group did not present a positive correlation with the sCD30 levels pretransplant (P = .54); in the post-transplant period, the 7- to 14-day samples showed patients with AR had higher levels of this biomarker (P = .036). The graft survival in 5 years of follow-up was not different between groups. CONCLUSIONS: The best time to predict AR using sCD30 is the 7- to 14-day sample; however, identifying and following the decrease of this biomarker from pre- to post-transplant seems to be better than just 1 measurement. The sCD30 post-transplant is another tool that may be used in monitoring patients after renal transplantation.
Assuntos
Rejeição de Enxerto/sangue , Sobrevivência de Enxerto/fisiologia , Antígeno Ki-1/sangue , Transplante de Rim/efeitos adversos , Adulto , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Valor Preditivo dos Testes , Período Pré-Operatório , Fatores de TempoRESUMO
Planned conversion from tacrolimus to sirolimus was evaluated in de novo kidney transplant recipients. In this multicenter, randomized, open-label study, 297 patients were initially treated with tacrolimus, mycophenolate sodium and prednisone. Of the 283 patients reaching 3 months, 97 were converted to sirolimus (SRL), 107 were maintained on tacrolimus (TAC) and 79 were patients receiving TAC without criteria to undergo intervention at month 3 (TACex). The primary objective was to show superior estimated glomerular filtration rate (eGFR) in the SRL group at month 24. Of the 258 patients who completed 24 months, 91 (94%) were in the SRL group, 101 (94%) in the TAC group and 66 (84%) in the TACex group. In the intention-to-treat population there were no differences in eGFR (66.2 ± 25.3 vs. 70.7 ± 25.1, p = 0.817) or in the severity of chronic sclerosing lesions scores in 24-month protocol biopsies. Higher mean urinary protein-to-creatinine ratio (0.36 ± 0.69 vs. 0.15 ± 0.53, p = 0.03) and higher incidence of treated acute rejection between months 3-24 (13.4% vs. 4.7%, p = 0.047) were observed in SRL compared to TAC group. In this population planned conversion from TAC to SRL 3 months after kidney transplantation was not associated with improved renal function at 24 months.
Assuntos
Rejeição de Enxerto/prevenção & controle , Transplante de Rim , Insuficiência Renal/terapia , Sirolimo/administração & dosagem , Tacrolimo/administração & dosagem , Adulto , Biópsia , Creatinina/sangue , Feminino , Taxa de Filtração Glomerular , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Ácido Micofenólico/análogos & derivados , Prednisona/administração & dosagem , Estudos Prospectivos , Sirolimo/efeitos adversos , Tacrolimo/efeitos adversos , Resultado do TratamentoRESUMO
Tumor necrosis factor-related apoptosis-inducing ligand-TNFSF10 (TRAIL), a member of the TNF-α family and a death receptor ligand, was shown to selectively kill tumor cells. Not surprisingly, TRAIL is downregulated in a variety of tumor cells, including BCR-ABL-positive leukemia. Although we know much about the molecular basis of TRAIL-mediated cell killing, the mechanism responsible for TRAIL inhibition in tumors remains elusive because (a) TRAIL can be regulated by retinoic acid (RA); (b) the tumor antigen preferentially expressed antigen of melanoma (PRAME) was shown to inhibit transcription of RA receptor target genes through the polycomb protein, enhancer of zeste homolog 2 (EZH2); and (c) we have found that TRAIL is inversely correlated with BCR-ABL in chronic myeloid leukemia (CML) patients. Thus, we decided to investigate the association of PRAME, EZH2 and TRAIL in BCR-ABL-positive leukemia. Here, we demonstrate that PRAME, but not EZH2, is upregulated in BCR-ABL cells and is associated with the progression of disease in CML patients. There is a positive correlation between PRAME and BCR-ABL and an inverse correlation between PRAME and TRAIL in these patients. Importantly, knocking down PRAME or EZH2 by RNA interference in a BCR-ABL-positive cell line restores TRAIL expression. Moreover, there is an enrichment of EZH2 binding on the promoter region of TRAIL in a CML cell line. This binding is lost after PRAME knockdown. Finally, knocking down PRAME or EZH2, and consequently induction of TRAIL expression, enhances Imatinib sensibility. Taken together, our data reveal a novel regulatory mechanism responsible for lowering TRAIL expression and provide the basis of alternative targets for combined therapeutic strategies for CML.
Assuntos
Antígenos de Neoplasias/metabolismo , Proteínas de Ligação a DNA/metabolismo , Leucemia Mielogênica Crônica BCR-ABL Positiva/metabolismo , Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Fatores de Transcrição/metabolismo , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Antígenos de Neoplasias/análise , Antineoplásicos/uso terapêutico , Benzamidas , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Carcinoma/tratamento farmacológico , Carcinoma/genética , Carcinoma/metabolismo , Linhagem Celular , Proteínas de Ligação a DNA/análise , Progressão da Doença , Proteína Potenciadora do Homólogo 2 de Zeste , Proteínas de Fusão bcr-abl/análise , Proteínas de Fusão bcr-abl/metabolismo , Humanos , Mesilato de Imatinib , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Melanoma/tratamento farmacológico , Melanoma/genética , Melanoma/metabolismo , Piperazinas/uso terapêutico , Complexo Repressor Polycomb 2 , Regiões Promotoras Genéticas , Pirimidinas/uso terapêutico , Interferência de RNA , Ligante Indutor de Apoptose Relacionado a TNF/análise , Ligante Indutor de Apoptose Relacionado a TNF/genética , Fatores de Transcrição/análise , Células Tumorais Cultivadas , Regulação para CimaRESUMO
Purified phospholipase A2 (PLA2) enzymes from Bothrops jararacussu snake venom were examined to evaluate NIH 3T3 and COS7 fibroblast cytotoxicity, as well as muscle myotoxic and inflammatory activities. Separation of fractions Bj-VII (from BthTX-I; a Lys49 PLA2 homolog) and 6-1 and 6-2 (from BthTX-II; an Asp49 PLA2) from B. jararacussu snake venom by SDS-PAGE in tricine buffer in the absence and presence of dithiothreitol revealed a homodimer with an estimated molecular mass of approximately 30 kDa (monomer mass approximately 15 kDa). This finding indicates that these toxins form dimeric complexes-a previously reported tendency among PLA2s. These toxins were assayed for viability with the MTT assay, which is used to examine the effects of phospholipases on the mitochondrial viability of cells. The toxins were also assayed for cytolysis of the fibroblast cell lines NIH 3T3 and COS7 by quantification of lactate dehydrogenase released into the medium. The results indicate that the PLA2s 6-1, 6-2 and the Bj-VII PLA2 homolog studied here induce moderate footpad edema and local myotoxicity. Moreover, exposure to these phospholipases led to a reduction in fibroblast viability; at the 1 muM dose of PLA2 tested, a reduction of 50% in cell viability was observed. The present findings indicate that the inflammatory activity observed in envenomation may be correlated with the cytotoxicity observed in fibroblasts.
Assuntos
Bothrops , Sobrevivência Celular/efeitos dos fármacos , Venenos de Crotalídeos , Edema/induzido quimicamente , Fibroblastos/efeitos dos fármacos , Fosfolipases A2 do Grupo II/isolamento & purificação , Fosfolipases A2 do Grupo II/toxicidade , Mitocôndrias/efeitos dos fármacos , Músculos/efeitos dos fármacos , Proteínas de Répteis/toxicidade , Animais , Células COS , Chlorocebus aethiops , Membro Posterior , Inflamação/induzido quimicamente , Camundongos , Células NIH 3T3 , Estrutura Quaternária de Proteína , Homologia de Sequência de Aminoácidos , Mordeduras de SerpentesRESUMO
Lectins are polyvalent carbohydrate-binding proteins of non-immune origin. Recently, we have isolated and characterized a lectin from the venom of the snake Bothrops jararacussu. This lectin (BJcuL) has been shown to bind to lactose moieties and induce agglutination of erythrocytes. In the present work, we observed that cells from human metastatic breast cancer (MDA-MB-435) and human ovarian carcinoma (OVCAR-5) cell lines adhere, although weakly, to BJcuL. However, BJcuL did not inhibit adhesion of these cells to the extracellular matrix proteins fibronectin, laminin and type I collagen. Importantly, viability of these tumor cells and cells from other human tumor cell lines and a bovine brain endothelial cell line was suppressed by BJcuL. These findings suggest that the lectin BJcuL may serve as an interesting tool for combating tumor progression by inhibiting tumor cell and endothelial cell growth.
Assuntos
Adesão Celular , Divisão Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Venenos de Crotalídeos/química , Venenos de Crotalídeos/farmacologia , Proteínas da Matriz Extracelular/metabolismo , Lectinas/química , Animais , Vasos Sanguíneos/citologia , Bothrops , Encéfalo/citologia , Neoplasias da Mama/patologia , Carcinoma/patologia , Bovinos , Colágeno/metabolismo , Venenos de Crotalídeos/análise , Relação Dose-Resposta a Droga , Endotélio Vascular/citologia , Feminino , Fibronectinas/metabolismo , Glioblastoma/patologia , Humanos , Laminina/metabolismo , Lectinas/análise , Lectinas/isolamento & purificação , Leucemia/patologia , Metástase Neoplásica/patologia , Neoplasias Ovarianas/patologia , Células Tumorais Cultivadas , Neoplasias da Bexiga Urinária/patologiaRESUMO
In a greenhouse experiment Brachiaria brizantha Stapf, cv. Marandu was grown in a nutrient solution. The treatments were a complete nutrient solution, nutrient solutions with the omissions of each macronutrient (N, P, K, Ca, Mg and S) and a control (with the omission of all macronutrients). Plants were harvested 50 days after transplanting. Dry matter yield, tiller number and plant height were recorded, and nutrient concentrations in shoot and root were determined. Omissions of N and P were the most limiting for plant growth, whereas K and Ca did not affect grass growth and tillering. Mg and S omissions resulted in significant decreases in the plant parameters. Great decreases in plant nutrient concentrations were verified in the treatments with nutrient omissions in solution. Visual symptoms of deficiencies were observed for each nutrient omission treatment, with those of N and P being the first and that of Ca being the latest shown by the plants. Studies on forms and sources of nutrients for nutrient solution to be used with this grass are suggested.
Em experimento de casa de vegetação, cultivou-se Brachiaria brizantha Stapf. cv. Marandu em solução nutritiva, tendo como tratamentos a solução completa, as omissões individuais de N, P, K, Ca, Mg, S e a testemunha (com omissão dos macronutrientes). Fez-se o acompanhamento da manifestação dos sintomas visuais de deficiência e, 50 dias após o transplante, avaliou-se a produção de matéria seca (MS), número de perfilhos (NP), a altura das plantas (H), bem como a composição mineral da parte aérea e das raízes. As omissões de N e P limitaram o crescimento, ao passo que a omissão de K não afetou a produção de MS e NP. A omissão de Ca não trouxe, para o período considerado, restrições na produção de MS, NP e H. Nas omissões de Mg e S as plantas tiveram fraco desempenho, superando apenas os tratamentos onde foram omitidos o N e o P. A composição mineral da parte aérea só apresentou diferenças acentuadas nos teores para os nutrientes omitidos. Sintomas visuais de deficiência foram observados para todas as omissões, sendo os primeiros manifestados através da omissão do N e do P e os últimos, através da omissão do Ca. São sugeridos estudos para melhor definição do balanço entre formas e fontes de nutrientes para a solução nutritiva quando utilizada no cultivo de plantas de Brachiaria brizantha cv. Marandu.
RESUMO
In a greenhouse experiment Brachiaria brizantha Stapf, cv. Marandu was grown in a nutrient solution. The treatments were a complete nutrient solution, nutrient solutions with the omissions of each macronutrient (N, P, K, Ca, Mg and S) and a control (with the omission of all macronutrients). Plants were harvested 50 days after transplanting. Dry matter yield, tiller number and plant height were recorded, and nutrient concentrations in shoot and root were determined. Omissions of N and P were the most limiting for plant growth, whereas K and Ca did not affect grass growth and tillering. Mg and S omissions resulted in significant decreases in the plant parameters. Great decreases in plant nutrient concentrations were verified in the treatments with nutrient omissions in solution. Visual symptoms of deficiencies were observed for each nutrient omission treatment, with those of N and P being the first and that of Ca being the latest shown by the plants. Studies on forms and sources of nutrients for nutrient solution to be used with this grass are suggested.
Em experimento de casa de vegetação, cultivou-se Brachiaria brizantha Stapf. cv. Marandu em solução nutritiva, tendo como tratamentos a solução completa, as omissões individuais de N, P, K, Ca, Mg, S e a testemunha (com omissão dos macronutrientes). Fez-se o acompanhamento da manifestação dos sintomas visuais de deficiência e, 50 dias após o transplante, avaliou-se a produção de matéria seca (MS), número de perfilhos (NP), a altura das plantas (H), bem como a composição mineral da parte aérea e das raízes. As omissões de N e P limitaram o crescimento, ao passo que a omissão de K não afetou a produção de MS e NP. A omissão de Ca não trouxe, para o período considerado, restrições na produção de MS, NP e H. Nas omissões de Mg e S as plantas tiveram fraco desempenho, superando apenas os tratamentos onde foram omitidos o N e o P. A composição mineral da parte aérea só apresentou diferenças acentuadas nos teores para os nutrientes omitidos. Sintomas visuais de deficiência foram observados para todas as omissões, sendo os primeiros manifestados através da omissão do N e do P e os últimos, através da omissão do Ca. São sugeridos estudos para melhor definição do balanço entre formas e fontes de nutrientes para a solução nutritiva quando utilizada no cultivo de plantas de Brachiaria brizantha cv. Marandu.