RESUMO
There are few prospective studies on patients with post-essential thrombocythemia myelofibrosis (PET-MF) and post-polycythemia vera myelofibrosis (PPV-MF). Therefore, we conducted a nationwide longitudinal prospective survey to clarify the clinical characteristics of these diseases. A total of 197 PET-MF and 117 PPV-MF patients diagnosed between 2012 and 2021 were analyzed. The median age at diagnosis was 70.0 years for both diseases. The time from diagnosis of ET or PV to that of MF was 9.6 and 10.4 years, respectively, with no significant difference. Patients with PPV-MF had higher hemoglobin levels and white blood cell counts than those with PET-MF, whereas those with PET-MF had higher platelet counts than those with PPV-MF. Although splenomegaly was more frequent in patients with PPV-MF at diagnosis, there was no difference in the frequency of constitutional symptoms. Ruxolitinib was the most common treatment administered to 74.6% and 83.8% of patients with PET-MF and PPV-MF, respectively. Patients with PET-MF and PPV-MF had similar prognoses, with 3-year overall survival (OS) of 0.742 in PET-MF and 0.768 in PPV-MF patients. In both diseases, leukemic transformation was the leading cause of death, followed by infection. The 3-year OS for patients with PET/PPV-MF and primary MF diagnosed during the same period was 0.754 and 0.626, respectively, with no significant difference. This survey provides real-world clinical features and prognostic data on secondary myelofibrosis in the ruxolitinib era.
Assuntos
Policitemia Vera , Mielofibrose Primária , Trombocitemia Essencial , Humanos , Idoso , Policitemia Vera/complicações , Policitemia Vera/diagnóstico , Policitemia Vera/terapia , Trombocitemia Essencial/complicações , Trombocitemia Essencial/diagnóstico , Trombocitemia Essencial/tratamento farmacológico , Mielofibrose Primária/diagnóstico , Mielofibrose Primária/etiologia , Mielofibrose Primária/tratamento farmacológico , Estudos ProspectivosRESUMO
INTRODUCTION: Chromosomal abnormalities (CAs) have been identified as important factors in determining the biological features and prognostic value of multiple myeloma (MM). MYC gene-related abnormalities (MYC GAs) are one of the CAs, but their unfavorable impact has not been fully investigated in daily clinical practice. METHODS: This study retrospectively analyzed the prognostic impact of MYC GAs on 81 patients through fluorescence in situ hybridization analysis in our institute. RESULTS: MYC GAs were associated with poor overall survival (hazard ratio [HR], 3.08; 95% confidence interval [CI]: 1.23-7.73; p = 0.017), progression-free survival (PFS) (HR, 2.96; 95% CI: 1.58-5.53; p < 0.001), and time to next treatment (TNT) (HR, 2.11; 95% CI: 1.13-3.93; p = 0.018) in the median follow-up of 34.7 months. Furthermore, MYC GAs with an additional chromosome 8 (MYC-Ch8(+)) were associated with shorter PFS (HR, 3.15; 95% CI: 1.38-7.2; p = 0.0064), whereas MYC GAs without an additional chromosome 8 (MYC-Ch8(-)) were associated with shorter PFS (HR, 3.62; 95% CI: 1.51-8.68; p = 0.004) and shorter TNT (HR, 3.72; 95% CI: 1.41-9.81; p = 0.0078). CONCLUSION: These findings could help identify high-risk patients with MM. Further prospective studies are needed to confirm the significance of MYC GAs for the MM prognostic effect.
Assuntos
Mieloma Múltiplo , Humanos , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/genética , Mieloma Múltiplo/tratamento farmacológico , Genes myc , Prognóstico , Hibridização in Situ Fluorescente , Estudos Retrospectivos , Aberrações CromossômicasRESUMO
Monocyte-derived fibrocytes recently garnered attention because the novel pathogenesis of myelofibrosis (MF), and suppression of fibrocyte differentiation by serum amyloid P remarkably improved MF. We previously revealed that human fibrocytes highly expressed signaling lymphocytic activation molecule F7 (SLAMF7) compared with macrophages and that SLAMF7high monocytes in the peripheral blood (PB) of MF patients were significantly elevated relative to those in healthy controls (HCs). In this study, we evaluated SLAMF7high monocyte percentage in the PB of HCs, myeloproliferative neoplasm (MPN) patients with MF, and MPN patients without MF by using a cross-sectional approach. We found that MPN patients with MF who harbored JAK2V617F had a significantly elevated SLAMF7high monocyte percentage, which correlated positively with the JAK2V617F allele burden. In addition, the serum concentration of interleukin-1ra (IL-1ra) was significantly correlated with the SLAMF7high monocyte percentage and JAK2V617F allele burden. These findings suggest that both SLAMF7high monocytes and IL-1ra could be useful noninvasive markers of MF onset. Furthermore, the JAK2V617F allele burden of SLAMF7high monocytes was significantly higher than that of SLAMF7low monocytes and could be a potential target of elotuzumab (Elo), an anti-SLAMF7 antibody used for treating multiple myeloma. Elo independently inhibited differentiation of fibrocytes derived not only from HCs but also from MF patients in vitro. Elo also ameliorated MF and splenomegaly induced by romiplostim administration in humanized NOG mice. In conclusion, an increase of SLAMF7high monocytes with higher JAK2V617F allele burden was associated with the onset of MF in MPN patients harboring JAK2V617F, and Elo could be a therapeutic agent for MPN patients with MF who harbor JAK2V617F.
Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Janus Quinase 2/genética , Monócitos/patologia , Mielofibrose Primária/tratamento farmacológico , Mielofibrose Primária/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Substituição de Aminoácidos , Contagem de Células Sanguíneas , Proliferação de Células , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Monócitos/metabolismo , Mutação de Sentido Incorreto , Fenilalanina/genética , Mielofibrose Primária/sangue , Mielofibrose Primária/patologia , Família de Moléculas de Sinalização da Ativação Linfocitária/metabolismo , Valina/genéticaRESUMO
Recently, monocyte-derived fibroblast-like cells, called fibrocytes, garnered attention as involved in the novel pathogenesis of various fibrotic diseases. They also play a role in the induction of myelofibrosis (MF). Neoplastic fibrocytes are overrepresented in the bone marrow of patients with primary MF, and the suppression of fibrocyte differentiation by serum amyloid P has been shown to remarkably improve MF. Further, thrombopoietin (TPO) or a TPO receptor agonist directly induces fibrocyte differentiation, and fibrocyte elimination reversed the MF phenotype in a murine model. Human fibrocytes highly express signaling lymphocytic activation molecule-F7 (SLAMF7) compared with macrophages. Myeloproliferative neoplasm (MPN) patients harboring JAK2V617F with MF had a significantly elevated SLAMF7high monocyte percentage, which correlated positively with the JAK2V617F allele burden. Furthermore, the JAK2V617F allele burden and the tendency to differentiate into fibrocytes of SLAMF7high monocytes was significantly higher than that of JAK2V617Flow monocytes and could be a potential target of elotuzumab (Elo), an anti-SLAMF7 antibody used to treat multiple myeloma. Elo independently inhibited the differentiation of fibrocytes derived not only from healthy controls but also from MF patients in vitro. Elo also ameliorated MF and splenomegaly induced by romiplostim administration in humanized NOG mice. Thus, Elo could be a therapeutic agent for MPN patients harboring JAK2V617F with MF.
Assuntos
Transtornos Mieloproliferativos , Mielofibrose Primária , Animais , Medula Óssea , Humanos , Macrófagos , Camundongos , MonócitosRESUMO
This retrospective study evaluated the outcomes of patients treated with combination of bendamustine and rituximab (BR) for recurrent indolent B-cell lymphoma from January 2011 to February 2018 in our department. The cohort included 36 males and 27 females, and majority of the patients (59%) were between 51 and 70 years of age. The disease types were follicular lymphoma (FL) and mantle-cell lymphoma in 42 (67%) and 15 (24%) patients, respectively. Median progression-free survival (PFS) was not reached in patients with FL who completed BR therapy. The analysis of patients who received BR therapy revealed that the number of CD4-positive lymphocytes remained around 200/µl even five years after the end of treatment. BR therapy was a useful treatment option for recurrent indolent B-cell lymphoma, especially in patients with FL, and completion of BR therapy appeared to be important for improved PFS. Furthermore, attention should be paid for potential infections for at least five years after BR therapy because cell-mediated immunodeficiency may become apparent after treatment.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma de Células B , Idoso , Cloridrato de Bendamustina , Feminino , Humanos , Linfoma de Células B/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estudos Retrospectivos , RituximabRESUMO
A 69-year-old woman presented to National Defense Medical College hospital for suspected nephrotic syndrome due to weight gain of 30 kg in 3 weeks and bilateral lower leg edema. However, her urinalysis showed microproteinuria, which excluded nephrotic syndrome. Computed tomography revealed severe systemic edema, pleural effusion, ascites, and enlarged cervical and axillary lymph nodes. Histological examination of axillary lymph node specimen showed a typical architecture of angioimmunoblastic T-cell lymphoma. One course of CHOP chemotherapy regimen was administered which improved the lymph nodes and systemic edema. The patient achieved complete remission after 6 courses of CHOP. Because serum vascular endothelial growth factor (VEGF) level was elevated before the treatment and normalized after the treatment, increased vascular permeability mediated by VEGF was hypothesized to have caused the systemic edema. In addition, VEGF secretion from Epstein-Barr virus (EBV)-infected cells was likely associated with the patient's clinical condition because B lymphocytes stained with CD20 were positive for Epstein-Barr virus-encoded small RNAs (EBERs) and VEGF.
Assuntos
Linfadenopatia Imunoblástica , Linfoma de Células T , Idoso , Edema , Feminino , Herpesvirus Humano 4 , Humanos , Fator A de Crescimento do Endotélio VascularRESUMO
M-CSF promotes the differentiation and survival of macrophages, and preferentially induces anti-inflammatory M2, rather than proinflammatory M1 macrophages. Recently, another cytokine, IL-32, was also shown to promote macrophage differentiation. In this article, we provide the first evidence, to our knowledge, that M-CSF has both additive and inhibitory effects on the macrophage-related activities of IL-32. When added to M-CSF-derived macrophages, M-CSF and IL-32 promoted macrophage survival, which was further enhanced by their combination. However, they had different effects on HIV-1 replication; that is, it was stimulated by M-CSF and inhibited by IL-32. Interestingly, the anti-HIV-1 activity of IL-32 was counteracted by M-CSF. Such inhibitory effect of M-CSF was not observed with IL-32-induced M1-like features including high cytokine/chemokine production and strong expression of the costimulatory molecule CD80. However, IL-32-treated macrophages unexpectedly showed also M2-like features including increased phagocytic activity, and high expression of CD14 and the scavenger receptor CD163, and the expression of CD14 and CD163 was further upregulated by cotreatment with M-CSF. The findings of this study regarding the unique functional interplay between M-CSF and IL-32 increase our understanding of the mechanisms that regulate the survival and M1/M2 ratio of macrophages, as well as HIV-1 replication in macrophages.
Assuntos
Infecções por HIV/imunologia , HIV-1/fisiologia , Interleucinas/imunologia , Fator Estimulador de Colônias de Macrófagos/imunologia , Macrófagos/imunologia , Replicação Viral/imunologia , Animais , Antígenos CD/imunologia , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/imunologia , Células Cultivadas , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/imunologia , Humanos , Fator Estimulador de Colônias de Macrófagos/farmacologia , Macrófagos/patologia , Macrófagos/virologia , Masculino , Fagocitose/efeitos dos fármacos , Fagocitose/imunologia , Replicação Viral/efeitos dos fármacosRESUMO
In order to produce petroleum alternatives from biomass, a significant amount of research has been focused on oils from microalgae due to their origin, which would not affect food availability. Nanoporous hybrid catalysts composed of ns Al2O3 and zeolites have been proven to be very useful compared to traditional catalysts in hydrotreating (HT), hydrocracking (HC), and catalytic cracking (CC) of large molecules. To evaluate the reaction scheme and products from model isoprenoid compounds of microalgae oil, nanoporous hybrid catalyst technologies (CC: ns Al2O3/H-USY and ns Al2O3/H-GaAlMFI; HC: [Ni-Mo/γ-Al2O3]/ns Al2O3/H-beta) were studied. The major product from CC on ns Al2O3/H-USY was highly aromatic gasoline, while the product from HC was half-isoparaffinic/olefinic kerosene. Although more than 50 wt% of the products from HT/CC on the USY catalyst was liquefied petroleum gas due to overcracking, the product from HT/CC on the MFI catalyst was high-octane-number gasoline. Delightfully, the product from HT/HC was kerosene and its average number was 11, with more than 80 wt% being isoparaffinic. As a result, it was demonstrated that hydrotreating may convert isoprenoid oil from microalgae over nanoporous hybrid catalysts into a variety of products.
Assuntos
Biocombustíveis , Nanoporos , Óleos/química , Terpenos/química , Óxido de Alumínio , Catálise , Microalgas , Modelos Biológicos , Temperatura , ZeolitasRESUMO
Oxidative stress is considered to be involved in the pathogenesis of primary blast-related traumatic brain injury (bTBI). We evaluated the effects of ascorbic acid 2-glucoside (AA2G), a well-known antioxidant, to control oxidative stress in rat brain exposed to laser-induced shock waves (LISWs). The design consisted of a controlled animal study using male 10-week-old Sprague-Dawley rats. The study was conducted at the University research laboratory. Low-impulse (54 Paâ¢s) LISWs were transcranially applied to rat brain. Rats were randomized to control group (anesthesia and head shaving, n = 10), LISW group (anesthesia, head shaving and LISW application, n = 10) or LISW + post AA2G group (AA2G administration after LISW application, n = 10) in the first study. In another study, rats were randomized to control group (n = 10), LISW group (n = 10) or LISW + pre and post AA2G group (AA2G administration before and after LISW application, n = 10). The measured outcomes were as follows: (i) motor function assessed by accelerating rotarod test; (ii) levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), an oxidative stress marker; (iii) ascorbic acid in each group of rats. Ascorbic acid levels were significantly decreased and 8-OHdG levels were significantly increased in the cerebellum of the LISW group. Motor coordination disorder was also observed in the group. Prophylactic AA2G administration significantly increased the ascorbic acid levels, reduced oxidative stress and mitigated the motor dysfunction. In contrast, the effects of therapeutic AA2G administration alone were limited. The results suggest that the prophylactic administration of ascorbic acid can reduce shock wave-related oxidative stress and prevented motor dysfunction in rats.
Assuntos
Ácido Ascórbico/análogos & derivados , Ataxia/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Animais , Ácido Ascórbico/farmacologia , Encéfalo/efeitos dos fármacos , Lesões Encefálicas Traumáticas/tratamento farmacológico , Cerebelo/efeitos dos fármacos , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
A pilot plant bioenergy recovery system from swine waste and garbage was constructed. A series of experiments was performed using swine feces (SF); a mixture of swine feces and urine (MSFU); a mixture of swine feces, urine and garbage (MSFUG); garbage and a mixture of urine and garbage (AUG). The system performed well for treating the source materials at a high organic loading rate (OLR) and short hydraulic retention time (HRT). In particular, the biogas production for the MSFUG was the highest, accounting for approximately 865-930 L kg(-1)-VS added at the OLR of 5.0-5.3 kg-VS m(-3) day(-1) and the HRT of 9 days. The removal of VS was 67-75%, and that of COD was 73-74%. Therefore, co-digestion is a promising method for the recovery of bioenergy from swine waste and garbage. Furthermore, the results obtained from this study provide fundamental information for scaling up a high-performance anaerobic system in the future.
Assuntos
Reatores Biológicos , Fontes Geradoras de Energia , Resíduos de Alimentos , Esterco , Anaerobiose , Animais , Fermentação , Metano/metabolismo , Projetos Piloto , Suínos , Urina , Eliminação de Resíduos Líquidos/métodosRESUMO
Acute graft-versus-host disease (GVHD) is a major cause of morbidity and mortality in allogeneic hematopoietic cell transplantation (allo-HCT). Majority of the current immunosuppressive strategies targeting donor T cells to prevent or treat acute GVHD are only partially effective, and often require escalated immunosuppressive therapy. Recent studies have revealed that activation of antigen-presenting cells in the proinflammatory milieu is important for the priming and promotion of GVHD. This activation is mediated by innate immune signaling pathways, which therefore potentially represent new targets in addressing GVHD. Using gene expression analysis of peripheral monocytes from patients' post-allo-HCT, we detected an upregulation of TGF-ß-activated kinase 1 (TAK1), a key regulator of the toll-like receptor signaling pathway. 5Z-7-oxozeaenol, a selective inhibitor of TAK1, reduced proinflammatory cytokine production by activated monocytes under lipopolysaccharide stimulation and T cell proliferation in allogeneic-mixed leukocyte reactions with monocyte-derived dendritic cells. In an experimental mouse model of GVHD, 5Z-7-oxozeaenol administration after allo-HCT ameliorated GVHD severity and mortality, with significant reduction in serum TNFα, IL-1ß, and IL-12 levels. Our findings suggest that altering the activation status of innate immune cells by TAK1 inhibition may be a novel therapeutic approach for acute GVHD.
Assuntos
Inibidores Enzimáticos/administração & dosagem , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas , Lactonas/administração & dosagem , MAP Quinase Quinase Quinases/antagonistas & inibidores , Terapia de Alvo Molecular , Resorcinóis/administração & dosagem , Doença Aguda , Adulto , Idoso , Aloenxertos , Animais , Modelos Animais de Doenças , Feminino , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/mortalidade , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Taxa de SobrevidaRESUMO
Glucocorticoid (GC) therapy occasionally relieves tumor-related fever and promotes tumor reduction in patients with chronic myelomonocytic leukemia (CMML). A mutation analysis of 24 patients with CMML revealed the relationship of GC effectiveness, defined as a monocyte reduction of > 50% within 3 days of methylprednisolone administration, with the MEFV single-nucleotide variant (SNV) and CBL mutation. Lipopolysaccharide-stimulated monocytes harboring MEFV E148Q produced greater amounts of IL-1ß and TNF-α than did wild-type monocytes; this was effectively suppressed by GC. Primary CMML cells harboring the MEFV SNV and CBL mutation, and the myelomonocytic leukemia cell line GDM-1, harboring the CBL mutation, were both more significantly suppressed than non-mutated cells following GC treatment in the presence of GM-CSF. A loss-of-function CBL mutation prolonged STAT5 phosphorylation after GM-CSF stimulation, which was rapidly terminated in both patient samples and GDM-1 cells. In conclusion, GC therapy effectively treats CMML cells harboring the MEFV SNV and CBL mutation by reducing inflammatory cytokine production and terminating prolonged STAT5 phosphorylation in the GM-CSF signaling pathway.
Assuntos
Glucocorticoides/administração & dosagem , Leucemia Mielomonocítica Crônica/tratamento farmacológico , Leucemia Mielomonocítica Crônica/genética , Leucemia Mielomonocítica Crônica/patologia , Mutação com Perda de Função/genética , Metilprednisolona/administração & dosagem , Polimorfismo de Nucleotídeo Único/genética , Proteínas Proto-Oncogênicas c-cbl/genética , Pirina/genética , Citocinas/metabolismo , Previsões , Glucocorticoides/farmacologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos , Humanos , Mediadores da Inflamação/metabolismo , Leucemia Mielomonocítica Crônica/metabolismo , Metilprednisolona/farmacologia , Fosforilação/genética , Fator de Transcrição STAT5/metabolismo , Transdução de Sinais , Células Tumorais CultivadasRESUMO
Mucosal-associated invariant T (MAIT) cells help protect against certain infections and are related to some autoimmune diseases. Immune thrombocytopenia (ITP) is a relatively rare hematological autoimmune disease associated with low platelet count. We designed a cross-sectional study wherein we examined peripheral blood samples of patients with ITP for the number of MAIT cells (CD3+TCR-Vα7.2+CD161+IL-18Rα+ lymphocytes) and their CD4/8 subsets (by flow cytometry) and levels of cytokines (by multiplex assays). The study cohort included 18 patients with ITP and 20 healthy controls (HCs). We first compared the number of MAIT cells between HCs and patients with ITP and then performed subgroup analysis in patients with ITP. The number of total MAIT cells in patients with ITP was significantly lower than that in HCs (p < 0.0001), and the CD4-CD8+ subset of MAIT cells showed the same trend. Moreover, patients with ITP refractory to prednisolone exhibited a significantly lower number of total MAIT and CD4-CD8+ MAIT cells than patients sensitive to prednisolone. The number of total MAIT and CD4-CD8+ MAIT cells was not correlated with the response to thrombopoietin receptor agonist treatment or with Helicobacter pylori infection. We found no relation between cytokine levels and response to prednisolone treatment, although the levels of IP-10 and RANTES showed a correlation with the number of total MAIT and CD4-CD8+ MAIT cells. In conclusion, total MAIT and CD4-CD8+ MAIT cells in peripheral blood were decreased in patients with ITP, correlating with their response to prednisolone.
Assuntos
Células T Invariantes Associadas à Mucosa/efeitos dos fármacos , Células T Invariantes Associadas à Mucosa/imunologia , Prednisolona/uso terapêutico , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Púrpura Trombocitopênica Idiopática/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Quimiocina CCL5/sangue , Quimiocina CXCL10/sangue , Estudos de Coortes , Estudos Transversais , Citocinas/sangue , Feminino , Glucocorticoides/uso terapêutico , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Células T Invariantes Associadas à Mucosa/patologia , Púrpura Trombocitopênica Idiopática/sangue , Subpopulações de Linfócitos T/efeitos dos fármacos , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/patologia , Resultado do TratamentoRESUMO
Sudden blast phase (SBP) is a rare event in which patients with chronic myeloid leukemia (CML) in complete cytogenetic response (CCyR) rapidly progress to the blast phase. Few patients on second-generation tyrosine kinase inhibitors (2nd TKIs) have been reported to develop SBP. Here, we report a 45-year-old man diagnosed with CML in the chronic phase in April 2008 and immediately started on imatinib therapy. He achieved CCyR 12 months after starting imatinib therapy. Imatinib was followed by treatment with the 2nd TKIs nilotinib and dasatinib from January 2011 to yield a better response. He achieved major molecular response (MMR) during dasatinib therapy in February 2012, but did not tolerate dasatinib well; hence, he was switched to nilotinib in July 2012. In December 2015, he presented at our hospital with fever and lumbago. A complete blood count revealed a white blood cell count of 30,500/µL with 60% blasts, leading to diagnosis of SBP. After dasatinib therapy and conventional chemotherapy, he again achieved MMR. This case demonstrates that SBP may occur after achieving MMR on treatment with 2nd TKIs. Continuous careful monitoring is required for the early detection of SBP, even in patients who have achieved MMR.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Crise Blástica , Substituição de Medicamentos/efeitos adversos , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/efeitos adversos , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversos , Dasatinibe/administração & dosagem , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos , Humanos , Mesilato de Imatinib/administração & dosagem , Masculino , Pessoa de Meia-Idade , Proteínas Tirosina Quinases/antagonistas & inibidores , Resultado do TratamentoRESUMO
Electrochemical treatment of the anaerobic digestion effluents using a Ti/Pt-IrO(2) electrode was evaluated in this study. The effects of electric current, NaCl dosage, and initial pH on ammonia, nitrate, total organic carbon (TOC), inorganic carbon (IC), final pH, and turbidity variations were studied in a series of batch experiments. It was found that the electric current and NaCl dosage had a considerably larger effect on the oxidization of ammonia; this was less for the effect of the initial pH. In addition, electroflotation was the main mechanism for turbidity, TOC, and IC removals. Further, the IC removal was mainly affected by the pH of wastewater. The electrochemical treatment using Ti/Pt-IrO(2) electrode without pretreatment was feasible for the anaerobic digestion effluent.
Assuntos
Irídio/química , Platina/química , Titânio/química , Eliminação de Resíduos Líquidos/instrumentação , Eliminação de Resíduos Líquidos/métodos , Anaerobiose , Eletroquímica , Eletrodos , Concentração de Íons de Hidrogênio , Cinética , Cloreto de SódioRESUMO
In order to find the optimal running conditions and mechanisms of ammonia removal through a soil trench system that is designed for treating pretreated methane fermentation effluent, a soil column whose structure was similar to the soil trench system was prepared, and irrigated with wastewater below 30 degrees C. At the beginning, ammonia was mainly adsorbed by the soils, and the ammonia adsorption capacity of soils gradually saturated. After the 12th day, nitrification began in the soil column; the ammonia in the soil column decreased sharply, and the nitrite and nitrate peak appeared sequentially as the wastewater application rate decreased from 0.74 to 0.37 l h(-1). When the nitrification in the soil column reached a steady-state, 98% of all the ammonia in the influent was transformed into nitrate. By changing the running conditions such as temperature, aeration, and wastewater application rate, it was found that the ammonia removal efficiency can be improved by aeration and impeded by low temperature. In these three variables, wastewater application rate has much greater affect on the ammonia removal efficiency; a lower wastewater application rate can increase the ammonia removal efficiency substantially because of the longer travel time.
Assuntos
Amônia/química , Solo/análise , Eliminação de Resíduos Líquidos/métodos , Poluentes Químicos da Água/química , Poluição da Água/prevenção & controle , Adsorção , Fermentação , Cinética , Metano/química , Nitratos/análise , Nitritos/análise , Temperatura , Eliminação de Resíduos Líquidos/instrumentaçãoRESUMO
In this study, ammonia stripping was optimized for pretreating anaerobic digestion effluent from an anaerobic digestion plant, and the possibility of using CO(2) stripping and biogas injection for adjusting the pH of the effluent before and after the ammonia stripping process was also investigated. For ammonia stripping, the results showed that an overdose of calcium hydroxide, i.e., 27.5g/L wastewater, achieved higher ammonia, phosphorus, chemical oxygen demand, suspended solids, and turbidity removal efficiency. An air flow rate of 5L/min for 1L of wastewater was thought as suitable for engineering application. The pH of the anaerobic digestion effluent can be increased from about 7 to about 9 by CO(2) stripping, however which is insufficient for ammonia stripping. For 1L of wastewater treated after ammonia stripping, the pH can be neutralized to about 7 from greater than 11 through biogas injection at 1L/min for less than 30min, and continuous injection does not decrease the pH. It was roughly estimated that 43m(3) of biogas (CH(4):CO(2) approximately 60%:40%) produced daily could be purified to CH(4):CO(2) approximately 74%:26% by neutralizing the pH of the 5m(3) anaerobic digestion effluent pretreated by ammonia stripping.
Assuntos
Amônia/química , Bactérias Anaeróbias/fisiologia , Reatores Biológicos , Esgotos/microbiologia , Eliminação de Resíduos Líquidos/métodos , Anaerobiose , Dióxido de Carbono/química , Técnicas de Química Analítica , Concentração de Íons de Hidrogênio , Esgotos/química , Microbiologia da ÁguaRESUMO
Here we investigated a biological association of constitutively active Src with TrkA in SK-N-MC human neuroblastoma cells. Activation of TrkA and extracellular signal-regulated kinase (ERK) by nerve growth factor (NGF) was inhibited by pretreatment with PP2, an inhibitor of Src family kinases. Moreover, NGF-induced phosphorylation of TrkA and ERK was also attenuated by the transfection with a dominant-negative src construct. On the other hand, the transfection with a constitutively active src construct enhanced these phosphorylations. In addition, we showed that active Src phosphorylates TrkA directly in vitro, and that Src associates with TrkA through Grb2 after NGF stimulation. These results suggest that constitutively active Src that associates with TrkA through Grb2 after NGF stimulation participates in TrkA phosphorylation and in turn enhances the mitogen-activated protein kinase signaling in SK-N-MC cells.
Assuntos
Sistema de Sinalização das MAP Quinases , Fator de Crescimento Neural/metabolismo , Neuroblastoma/metabolismo , Receptor trkA/metabolismo , Transdução de Sinais , Quinases da Família src/metabolismo , Western Blotting , Linhagem Celular Tumoral , Eletroforese em Gel de Poliacrilamida , Ativação Enzimática , Inibidores Enzimáticos/farmacologia , Humanos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Neuroblastoma/patologia , Fosforilação , Proteínas Tirosina Quinases/antagonistas & inibidores , RNA/isolamento & purificação , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transfecção , Domínios de Homologia de src , Quinases da Família src/genéticaRESUMO
The edible mushroom Agaricus blazei Murill is considered a health food in many countries after it was reported to be a source of antitumor and immunoactive compounds. An aqueous extract (AE) from this basidiomycete significantly enhanced the expression of the c-Jun/activator protein-1 (AP1) in the human breast cancer cell line MCF7. Incubating the cells with 17-beta-estradiol (E2), p-nonylphenol (NP), and the AE combined, or NP plus the AE, resulted in increased cell proliferation compared to the untreated control by 93 and 67%, respectively. However, incubating the cells with the extract alone did not enhance cell division. It is suggested that the enhanced proliferation of MCF7 cells in the presence of NP and the AE may be due to the involvement of an AP1 gene regulatory complex. This is the first report showing enhanced c-Jun/AP1 expression in MCF7 cells incubated with an aqueous fungal extract.