RESUMO
BACKGROUND: Prenatal diagnosis of congenital heart disease (CHD) often leads affected families to experience psychological stress. Pediatric cardiology consultation is important in providing parents with sufficient information and reducing their anxiety to make an informed pregnancy decision. Involving a fetal nurse coordinator may optimize fetal anomaly care. Our study aimed to identify factors associated with parental decision-making for choosing to use pediatric cardiology consultations and pregnancy termination. METHODS: From September 2017 to December 2018, all fetal CHD cases diagnosed in the second trimester from a primary screening clinic in Taiwan were included (n = 145). Univariate and multivariate logistic regression were performed to analyze maternal, fetal, and medical factors for predictors of parental decisions for consultation use and pregnancy termination. RESULTS: Acceptance for fetal nurse coordinator care and pediatric cardiology consultation were 84.8% (n = 123) and 83.4% (n = 121), respectively. Predictors for termination of pregnancy included the following: multiple anomalies (OR: 10.6; 95% CI: 3.6-35.7), chromosomal/genetic abnormalities (OR: 20.2; 95% CI: 3.1-395.8), severe CHDs (OR: 9.8; 95% CI: 4.3-23.4), CHDs that required surgery (OR: 32.4; 95% CI: 11.4-117.8), and physiological single-ventricle (OR: 47.3; 95% CI: 12.4-312.5). Parents who had pediatric cardiology counseling were less likely to terminate the pregnancy (OR: 0.1; 95% CI: 0.0-0.7). Parents with fetal diagnosis having multiple anomalies (OR: 0.2; 95% CI: 0.1-0.7) or chromosomal/genetic abnormalities (OR: 0.1; 95% CI: 0.03-0.9) were less likely to make use of cardiology consultation. Parents who accepted fetal nurse coordinator care were more likely to have pediatric cardiology consultation before pregnancy decision (OR: 149.5, 95% CI: 37.8-821.5). CONCLUSIONS: Anomaly complexity appeared to be a strong predictor for termination of pregnancy beyond non-acceptability of prenatal cardiology consultation. Prenatal cardiology counseling may help support the parental decision to continue with the pregnancy. Incorporation of a fetal nurse coordinator care into the multidisciplinary fetal medicine team improved the acceptability of prenatal consultation.
Assuntos
Aborto Induzido , Cardiopatias Congênitas , Gravidez , Feminino , Criança , Humanos , Diagnóstico Pré-Natal , Cardiopatias Congênitas/diagnóstico , Aberrações Cromossômicas , Pais/psicologia , Encaminhamento e Consulta , Ultrassonografia Pré-NatalRESUMO
BACKGROUND: Age variances in systemic lupus erythematosus (SLE) may reflect different patterns and consequences. Monocyte differentiation is critical, and cytokine and chemokine milieu may be associated with long term outcome and treatment responses. This study aims to evaluate the inflammatory cellular and serology pathways associated with age in our lupus registry. METHODS: We included patients with SLE and divided them into 2 groups according to age, ≤18 or >18 years old. We performed flow cytometry analysis to define the peripheral blood monocyte differentiation pattern and phenotypes and used the multiplex method to detect cytokine and chemokine panels. The results were then compared between the 2 subgroups. RESULTS: In total, 47 SLE patients were included in this study. Of those, 23 patients were 18 years old or younger, and 24 patients were over the age of 18 years old. An increased distribution of circulating Type 2b macrophage (M2b) subsets was found in patients over 18 years old (P < 0.01), and we found the Type 1 macrophage (M1) to demonstrate a marked increase in those patients ≤18 years old (P = .05). Eotaxin values were significantly higher in patients >18 years old (P = .03), and Macrophage Inflammatory Protein (MIP)-1alpha, MIP-1beta, Interleukine (IL)-1Ra, Interferon (IFN)-alpha2, IL-12, IL-13, IL-17A, IL-1beta, IL-2, IL-4, IL-5, IL-7, IL-9, Monocyte Chemoattractant Protein (MCP)-3, Transforming Growth Factor (TGF)-alpha, and Tumor necrosis factor (TNF)-beta were significantly higher in patients ≤18 years old (all P < .05). CONCLUSIONS: We found significant M2b polarization in adult SLE patients, and several cytokines and chemokines were significantly higher in SLE patients ≤ 18 years old. Peripheral blood mononuclear cell differentiation and cytokine milieu could represent composite harm from both Type 2 helper T cells (Th2) and Type 17 helper T cells (Th17) pathways and may thus be a potential therapeutic target in younger SLE patients.
Assuntos
Leucócitos Mononucleares , Lúpus Eritematoso Sistêmico , Quimiocinas , Citocinas , Humanos , Sistema de RegistrosRESUMO
BACKGROUND: Psoriatic arthritis (PSA) is a form of immune-mediated inflammatory arthritis that predominantly begins with enthesitis. Studying the gut microbiota of PSA patients may offer new insights into the pathogenesis of enthesitis, compared to other arthritis. We designed a prospective study to examine gut microbiome of patients with PSA, primarily with enthesitis and dactylitis, and compared the data with other undifferentiated types of arthritis (NO PSA) patients, without enthesitis or dactylitis. METHODS: We enrolled 9 PSA patients and 10 NO PSA patients in this study. We excluded rheumatoid arthritis, systemic lupus erythematosus, Sjogren syndrome, systemic sclerosis, mixed connective tissue disease, polymyositis, dermatomyositis, ANCA-associated vasculitis, and gouty arthritis patients. The fecal samples were investigated using 16S rRNA amplicon sequencing, followed by bioinformatics and statistical analyses. RESULTS: None of the available objective clinical laboratory data could differentiate PSA group from the NO PSA subgroup. The microbiota result shows that Family: XIII_AD3011 is significantly higher in NO PSA patients' than in PSA patients' stool samples (P = .039). Megasphaera elsdenii in the PSA group was 10,000 times higher than in the NO PSA group.Our results demonstrated high intragroup homogeneous and high intergroup heterogeneous microbiota. The clinical symptoms of either enthesitis or dactylitis are associated with higher presence of specific microbiota in the current study. The PSA and other undifferentiated arthritis could be differentiated with microbiota analysis. In the future, a larger cohort and thorough biochemical study are needed for confirmation.The microbiota is different between PSA and NO PSA patients, and the species could be used as a differential diagnostic tool between these 2 diseases. The clinically available serum markers may not be enough to reflect the details of patients with different patterns of arthritis. Megasphaera elsdenii species could be a link between gut flora and enthesitis and/or dactylitis clinically in PSA. We confirm the fact that the Bifidobacterium longum correlates negatively with eosinophils.
Assuntos
Artrite Psoriásica , Microbioma Gastrointestinal , Artrite Psoriásica/complicações , Artrite Psoriásica/diagnóstico , Humanos , Projetos Piloto , Estudos Prospectivos , RNA Ribossômico 16S/genéticaRESUMO
Occupational asbestos exposure was prevalent in Taiwan, but asbestos-related diseases (ARDs) have rarely been recognized. We conducted in-depth face-to-face interviews with 16 patients with ARDs. All of them had worked in industries known for high asbestos exposure. However, only three patients had filed workers' compensation (WC) claims, and of them, only two patients were approved. Reasons for the low compensation rate of ARDs could be divided into institutional barriers related to the flaws of the WC system and non-institutional barriers related to the knowledge status, causal interpretation, and social situations of individual workers. The Labor Occupational Accident Insurance and Protection Act passed in April 2021 has responded to the under-compensation of occupational diseases. However, the new act's effects toward improving the recognition of ARDs remain questionable. Our findings indicated that additional efforts are needed to remove non-institutional barriers hindering workers' ability to ensure their compensation rights.
Assuntos
Amianto , Doenças Profissionais , Síndrome do Desconforto Respiratório , Amianto/efeitos adversos , Humanos , Doenças Profissionais/epidemiologia , Taiwan/epidemiologia , Indenização aos TrabalhadoresRESUMO
OBJECTIVES: The goal of this analysis was to examine the comparative effectiveness of coronary artery bypass grafting versus percutaneous coronary intervention among patients aged less than 60 years. METHODS: We performed a multicenter, retrospective analysis of all cardiac revascularization procedures from 2005 to 2015 among 7 medical centers. Inclusion criteria were age less than 60 years and 70% stenosis or greater in 1 or more major coronary artery distribution. Exclusion criteria were left main 50% or greater, ST-elevation myocardial infarction, emergency status, and prior revascularization procedure. After applying inclusion and exclusion criteria, the final study cohort included 1945 patients who underwent cardiac surgery and 2938 patients who underwent percutaneous coronary intervention. The primary end point was all-cause mortality stratified by revascularization strategy. Secondary end points included stroke, repeat revascularization, and 30-day mortality. We used inverse probability weighting to balance differences among the groups. RESULTS: After adjustment, there was no significant difference in 30-day mortality (surgery: 0.8%; percutaneous coronary intervention: 0.7%, P = .86) for patients with multivessel disease. Patients undergoing surgery had a higher risk of stroke (1.3% [n = 25] vs 0.07% [n = 2], P < .001). Overall, surgery was associated with superior 10-year survival compared with percutaneous coronary intervention (hazard ratio, 0.71; 95% confidence interval, 0.57-0.88; P = .002). Repeat procedures occurred in 13.4% (n = 270) of the surgery group and 36.4% (n = 1068) of the percutaneous coronary intervention group, with both groups mostly undergoing percutaneous coronary intervention as their second operation. Accounting for death as a competing risk, at 10 years, surgery resulted in a lower cumulative incidence of repeat revascularization compared with percutaneous coronary intervention (subdistribution hazard ratio, 0.34; 95% confidence interval, 0.28-0.40; P < .001). CONCLUSIONS: Among patients aged less than 60 years with 2-vessel disease that includes the left anterior descending or 3-vessel coronary artery disease, surgery was associated with greater long-term survival and decreased risk of repeat revascularization.
Assuntos
Ponte de Artéria Coronária , Doença da Artéria Coronariana/terapia , Intervenção Coronária Percutânea , Fatores Etários , Pesquisa Comparativa da Efetividade , Ponte de Artéria Coronária/efeitos adversos , Ponte de Artéria Coronária/mortalidade , Doença da Artéria Coronariana/mortalidade , Humanos , New England , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/mortalidade , Sistema de Registros , Retratamento , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/etiologia , Fatores de Tempo , Resultado do TratamentoRESUMO
Acute Kidney Recovery (AKR) is a potential benefit of transcatheter aortic valve implantation (TAVI). We determined the incidence and predictors of AKR in a multicenter prospective registry of TAVI. After excluding patients on dialysis or who died within 48 hours postprocedure, we reviewed 1,502 consecutive patients underwent TAVI in Northern New England from 2012 to 2017. Patients were categorized into 3 groups based on the change in postprocedure estimated glomerular filtration rate (eGFR): Acute Kidney Injury (AKI, decrease in eGFR >25%), AKR (increase in eGFR >25%) or no change in kidney function on discharge creatinine following TAVI. We then focused in patients with baseline chronic kidney disease (CKD defined as eGFR ≤60 ml/min; nâ¯=â¯755) and developed multivariate predictor models to determine the clinical and procedural variables associated with AKR. For the TAVI cohort (nâ¯=â¯1,502), the overall incidence of AKR was 17.8%. AKR was threefold higher in patients with eGFR ≤60 ml/min as compared to those with eGFR >60 ml/min (26.6% vs 8.9%, p < 0.001). In the CKD population, hospital complications were similar among patients with no change in renal function and AKR; patients with AKI had a higher rate of hospital mortality, pacemaker implantation, length of hospitalization, and transfusions. Using multivariable logistic regression, moderate to severe lung disease, eGFR < 50 ml/min and previous aortic valve surgery were found to be independent predictors of AKR. Patients with diabetes mellitus, baseline anemia, and Society of thoracic surgeons score >6.1 were less likely to develop AKR. In conclusion, AKR occurred in 1 of 4 of all TAVI patients with baseline CKD and was a more frequent phenomena than AKI. Patients with decreased lung function, previous aortic valve surgery and worse baseline renal function were more likely to demonstrate AKR, whereas patients with diabetes mellitus, baseline anemia, and higher Society of thoracic risk scores were less likely to see improvements in renal function after TAVI.
Assuntos
Recuperação de Função Fisiológica , Insuficiência Renal Crônica/terapia , Substituição da Valva Aórtica Transcateter , Injúria Renal Aguda/etiologia , Idoso , Idoso de 80 Anos ou mais , Transfusão de Sangue/estatística & dados numéricos , Creatinina/análise , Feminino , Taxa de Filtração Glomerular , Mortalidade Hospitalar , Humanos , Tempo de Internação/estatística & dados numéricos , Pneumopatias/epidemiologia , Masculino , New England/epidemiologia , Marca-Passo Artificial , Sistema de Registros , Insuficiência Renal Crônica/epidemiologia , Substituição da Valva Aórtica Transcateter/efeitos adversosRESUMO
OBJECTIVE: To present an accurate prenatal diagnosis of coarctation of the aorta with ventricular septal defect and to illustrate how early diagnosis in prenatal period with proper referral and counseling can optimize management. CASE REPORT: A case with coarctation of the aorta with ventricle septal defect was found to have an abnormal three vessel view at 12 weeks, and with close follow-ups, coarctation of the aorta with ventricle septal defect was diagnosed at 24 weeks. Following the support from a multidisciplinary team that provided counseling, diagnosis, and follow-ups, the pregnant woman decided to continue with the pregnancy and had a vaginal delivery at a medical center. The newborn made an uneventful recovery after undergoing cardiac surgery on day 9. CONCLUSION: The case demonstrates the role a fetal medicine team plays in diagnosing, supporting, and seamlessly transferring the congenital heart disease case from the first line obstetrician to the cardiac surgeon. A multi-disciplinary team approach was able to lead to improved perinatal outcome of the congenital heart disease case.
Assuntos
Coartação Aórtica/diagnóstico por imagem , Comunicação Interventricular/diagnóstico por imagem , Coartação Aórtica/patologia , Coartação Aórtica/cirurgia , Feminino , Comunicação Interventricular/patologia , Comunicação Interventricular/cirurgia , Humanos , Lactente , Recém-Nascido , Equipe de Assistência ao Paciente , Gravidez , Ultrassonografia Doppler , Ultrassonografia Pré-NatalRESUMO
OBJECTIVE: There are no prospective randomized trial data to guide decisions on optimal revascularization strategies for patients with multivessel coronary artery disease and reduced ejection fraction. In this analysis, we describe the comparative effectiveness of coronary artery bypass grafting (CABG) versus percutaneous coronary intervention (PCI) in this patient population. METHODS: A multicenter, retrospective analysis of all CABG (n = 18,292) and PCIs (n = 55,438) performed from 2004 to 2014 among 7 medical centers reporting to the Northern New England Cardiovascular Disease Study Group. After applying inclusion and exclusion criteria from the Surgical Treatment for Ischemic Heart Failure trial, there were 955 CABG and 718 PCI patients with an ejection fraction ≤ 35% and 2- or 3-vessel disease. Inverse probability weighting was used for risk adjustment. The primary end point was all-cause mortality. Secondary end points included rates of 30-day mortality, stroke, acute kidney injury, and incidence of repeat revascularization. RESULTS: The median duration of follow-up was 4.3 years (range, 1.59-6.71 years). CABG was associated with improved long-term survival compared with PCI after risk adjustment (hazard ratio, 0.59; 95% confidence interval, 0.50-0.71; P < .01). Although CABG and PCI had similar 30-day mortality rates (P = .14), CABG was associated with a higher frequency of stroke (P < .001) and acute kidney injury (P < .001), whereas PCI was associated with a higher incidence of repeat revascularization (P < .001). CONCLUSIONS: Among patients with reduced ejection fraction and multivessel disease, CABG was associated with improved long-term survival compared with PCI. CABG should be strongly considered in patients with ischemic cardiomyopathy and multivessel coronary disease.
Assuntos
Ponte de Artéria Coronária , Isquemia Miocárdica/cirurgia , Intervenção Coronária Percutânea , Idoso , Idoso de 80 Anos ou mais , Pesquisa Comparativa da Efetividade , Ponte de Artéria Coronária/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/mortalidade , Intervenção Coronária Percutânea/mortalidade , Estudos Retrospectivos , Análise de SobrevidaRESUMO
Increasing evidence suggests that there is a unique cell subpopulation in melanoma that can form nonadherent melanospheres in serum-free stem cell medium, mimicking aggressive malignancy. Using melanospheres as a model to investigate progression mechanisms, we found that miR-519d overexpression was sufficient to promote cell proliferation, migration, invasion, and adhesion in vitro and lung metastatic capability in vivo The cell adhesion receptor EphA4 was determined to be a direct target of miR-519d. Forced expression of EphA4 reversed the effects of miR-519d overexpression, whereas silencing of EphA4 phenocopied the effect of miR-519d. Malignant progression phenotypes were also affected at the level of epithelial-to-mesenchymal transition and the ERK1/2 signaling pathway inversely affected by miR-519d or EphA4 expression. In clinical specimens of metastatic melanoma, we observed significant upregulation of miR-519d and downregulation of EphA4, in the latter case correlated inversely with overall survival. Taken together, our results suggest a significant functional role for miR-519d in determining EphA4 expression and melanoma progression.Significance: These results suggest a significant role for miR-519d in determining expression of a pivotal cell adhesion molecule that may impact risks of malignant progression in many cancers. Cancer Res; 78(1); 216-29. ©2017 AACR.
Assuntos
Melanoma/genética , Melanoma/patologia , MicroRNAs/genética , Receptor EphA4/genética , Regiões 3' não Traduzidas , Animais , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação para Baixo , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/secundário , Masculino , Camundongos SCID , Receptor EphA4/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: Toll-like receptor 4 (TLR4) is one of the best known TLR members expressed on the surface of several leukocytes and tissue cells and has a key function in detecting pathogen and danger-associated molecular patterns. The role of TLR4 in the pathophysiology of several age-related diseases is also well recognized, such as prostate cancer (PCa). TLR4 polymorphisms have been related to PCa risk, but the relationship between TLR4 genotypes and aggressive PCa risk has not been evaluated by any systematic reviews. METHODS: We performed a systematic review and meta-analysis of candidate-gene and genome-wide association studies analyzing this relationship and included only white population. Considering appropriate criteria, only nine studies were analyzed in the meta-analysis, including 3,937 aggressive PCa and 7,382 controls. RESULTS: Using random effects model, no significant association was found in the ten TLR4 SNPs reported by at least four included studies under any inheritance model (rs2737191, rs1927914, rs10759932, rs1927911, rs11536879, rs2149356, rs4986790, rs11536889, rs7873784, and rs1554973). Pooled estimates from another ten TLR4 SNPs reported by three studies also showed no significant association (rs10759930, rs10116253, rs11536869, rs5030717, rs4986791, rs11536897, rs1927906, rs913930, rs1927905, and rs7045953). Meta-regression revealed that study type was not a significant source of between-study heterogeneity. CONCLUSIONS: TLR4 polymorphisms were not significantly associated with the risk of aggressive PCa.
Assuntos
Predisposição Genética para Doença/genética , Imunidade Inata/genética , Polimorfismo de Nucleotídeo Único , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Receptor 4 Toll-Like/genética , Estudo de Associação Genômica Ampla , Humanos , Masculino , Neoplasias da Próstata/imunologiaRESUMO
A simple and mild catalytic coupling reaction of propargyl halides with organotitanium reagents is reported. The reaction of propargyl bromide with organo-titanium reagents mediated by NiCl2 (2 mol%) and PCy3 (4 mol%) in CH2Cl2 afforded coupling product allenes in good to excellent yields (up to 95%) at room temperature. However, NiCl2(PPh3)2 was the best catalyst for substituted propargyl halides to yield allenes or alkynes preferentially. On the basis of the experimental results, a possible catalytic cycle has been proposed.
Assuntos
Níquel/química , Compostos Organometálicos/química , Pargilina/análogos & derivados , Titânio/química , Alcenos/síntese química , Alcinos/síntese química , Catálise , Pargilina/química , TemperaturaRESUMO
PURPOSE: Glycine N-methyltransferase (GNMT) affects genetic stability by regulating the ratio of S-adenosylmethionine to S-adenosylhomocysteine, by binding to folate, and by interacting with environmental carcinogens. In Taiwanese men, GNMT was found to be a tumor susceptibility gene for prostate cancer. However, the association of GNMT with prostate cancer risk in other ethnicities has not been studied. It was recently reported that sarcosine, which is regulated by GNMT, increased markedly in metastatic prostate cancer. We hereby explored the association of GNMT polymorphisms with prostate cancer risk in individuals of European descent from the Health Professionals Follow-up Study (HPFS). METHODS: A total of 661 incident prostate cancer cases and 656 controls were identified from HPFS. The GNMT short tandem repeat polymorphism 1 (STRP1), 4-bp insertion/deletion polymorphisms (INS/DEL) and the single nucleotide polymorphism rs10948059 were genotyped to test for their association with prostate cancer risk. RESULTS: The rs10948059 T/T genotype was associated with a 1.62-fold increase in prostate cancer risk (95% confidence interval (CI): 1.18, 2.22) when compared with the C/C genotype. The STRP1 ≥ 16GAs/≥ 16GAs genotype was associated with decreased risk of prostate cancer when compared with the < 16GAs/< 16GAs genotype (odds ratio (OR)â= 0.68; 95% CI: 0.46, 1.01). INS/DEL was not associated with prostate cancer risk. Haplotypes containing the rs10948059 T allele were significantly associated with increased prostate cancer risk. CONCLUSION: In men of European descent, the GNMT rs10948059 and STRP1 were associated with prostate cancer risk. Compared to the study conducted in Taiwanese men, the susceptibility GNMT alleles for prostate cancer had a reverse relationship. This study highlights the differences in allelic frequencies and prostate cancer susceptibility in different ethnicities.
Assuntos
Glicina N-Metiltransferase/genética , Polimorfismo Genético , Neoplasias da Próstata/genética , Idoso , Povo Asiático , Seguimentos , Pessoal de Saúde/estatística & dados numéricos , Humanos , Mutação INDEL , Masculino , Repetições de Microssatélites , Pessoa de Meia-Idade , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/etnologia , Estados Unidos , População BrancaRESUMO
OBJECTIVE: To observe the effect of Tetramethyl pyrazine (TMP) on the cytokines and inflammatory mediators in the serum and the synovial fluid of collagen-induced arthritis (CIA)rats, and further to investigate its possible mechanisms for treating rheumatoid arthritis (RA). METHODS: Type II CIA rat model was established. Rats in the TMP group were administered with TMP at 50 mg/kg and 100 mg/kg, once daily. Dexamethasone at 2.0 mg/kg was intramuscularly injected to those in the Dexamethasone treated group, once daily. Normal saline at 2 mL/kg was given to those in the normal control group and the model group, once daily. All medication was started from the 7th day, lasting to the 35th day. CIA rats' foot swelling degree was observed. Contents of serum IL-1, IL-6, IL-2, NO and PGE2in the synovial fluid were detected by radioimmunoassay and nitrate reduction method. RESULTS: Compared with the normal group, the foot swelling obviously increased, contents of NO and PGE2 in the synovial fluid were obviously elevated in the model group (P < 0.01). Compared with the model group, the foot swelling could be obviously inhibited by 100 mg/kg TMP and Dexamethasone; serum levels of IL-1 and IL-6 obviously decreased, serum IL-2 level obviously increased, contents of NO and PGE, decreased (P < 0.01). TMP 50 mg/kg could obviously inhibit the foot swelling of CIA rats (P < 0.01). There was no statistical difference in other indices (P > 0.05). CONCLUSIONS: TMP at 100 mg/kg showed obvious inhibition on CIA rats. Its inhibitory effect might be correlated to inhibiting activities of endogenous cytokines and the generation of inflammatory mediators in inflammation local regions, improving contents of anti-inflammation cytokines, and inducing the balance of the inflammatory cytokine network.
Assuntos
Artrite Experimental/sangue , Artrite Experimental/metabolismo , Pirazinas/farmacologia , Animais , Dinoprostona/metabolismo , Feminino , Interleucina-1beta/sangue , Interleucina-2/sangue , Interleucina-6/sangue , Masculino , Óxido Nítrico/metabolismo , Ratos , Ratos Sprague-Dawley , Líquido Sinovial/metabolismoRESUMO
PURPOSE: Serum NGAL is highly expressed in patients with advanced renal cancer treated with sunitinib. We investigated the role of NGAL in sunitinib resistance in renal cell carcinoma to identify potential tactics to overcome it. MATERIALS AND METHODS: NGAL expression was correlated with sunitinib sensitivity. Vascular endothelial growth factor related upstream Ras, Erk1/2 and STAT1 phosphorylation activity in Caki-1 and NGAL transfected Caki-1 cells after sunitinib treatment was analyzed using Western blot. NGAL and vascular endothelial growth factor-A interaction with sunitinib therapeutic efficacy was monitored in renal cell carcinoma tumor xenografted mice by tumor growth inhibition, serum NGAL and vascular endothelial growth factor-a levels, and microscopic examination of tumor microvascular density. RESULTS: Sunitinib cytotoxicity in various renal cell carcinoma cell lines was reversibly related to NGAL expression. Sunitinib showed the lowest 50% inhibitory concentration (5.53 µM) in Caki-1 cells, which had the lowest NGAL expression of these renal cell carcinoma cell lines. After sunitinib treatment adding NGAL inhibited Ras and Erk1/2 phosphorylation but activated STAT1α phosphorylation in Caki-1 cells and Caki-1 cells transfected with NGAL. In a xenograft mouse model sunitinib significantly inhibited tumor growth in Caki-1 mice. NGAL transfected Caki-1 mice had higher serum NGAL and lower vascular endothelial growth factor-A than Caki-1 mice. Microvascular density was decreased in Caki-1 mice with sunitinib treatment. CONCLUSIONS: NGAL in tumor cells may show crosstalk with vascular endothelial growth factor-a and alternative activation in stimulating tumor growth during sunitinib treatment. It may become a therapeutic target to reverse sunitinib resistance in renal cell carcinoma.
Assuntos
Proteínas de Fase Aguda/fisiologia , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos , Indóis/farmacologia , Indóis/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Lipocalinas/fisiologia , Proteínas Proto-Oncogênicas/fisiologia , Pirróis/farmacologia , Pirróis/uso terapêutico , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Animais , Células Cultivadas , Lipocalina-2 , Masculino , Camundongos , Camundongos Nus , SunitinibeRESUMO
PURPOSE: In previous studies, we observed a positive association between Trichomonas vaginalis serostatus and risk of prostate cancer, particularly aggressive cancer, which we hypothesized might be due to T. vaginalis-mediated intraprostatic inflammation and cell damage. To explore this hypothesis further, we investigated effect modification by Toll-like receptor 4 (TLR4) variation on this association. We hypothesized that TLR4 variation might serve a marker of the anti-trichomonad immune response because T. vaginalis has been shown to elicit inflammation through this receptor. METHODS: We previously genotyped the non-synonymous TLR4 single nucleotide polymorphism (SNP), rs4986790, and determined T. vaginalis serostatus for 690 incident prostate cancer cases and 692 controls in a nested case-control study within the Health Professionals Follow-up Study. RESULTS: A non-significant suggestion of effect modification was observed by rs4986790 carrier status on the association between T. vaginalis serostatus and prostate cancer risk (p interaction = 0.07). While no association was observed among men homozygous wildtype for this SNP (odds ratio (OR) = 1.23, 95 % confidence interval (CI): 0.86-1.77), a positive association was observed among variant carriers (OR = 4.16, 95 % CI: 1.32-13.1). CONCLUSIONS: Although not statistically significant, TLR4 variation appeared to influence the association between T. vaginalis serostatus and prostate cancer risk consistent with the hypothesis that inflammation plays a role in this association. Larger studies will be necessary to explore this possible effect modification further.
Assuntos
Carcinoma/epidemiologia , Carcinoma/etiologia , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/etiologia , Receptor 4 Toll-Like/genética , Tricomoníase/complicações , Tricomoníase/epidemiologia , Adulto , Idoso , Carcinoma/sangue , Carcinoma/genética , Suscetibilidade a Doenças/epidemiologia , Modificador do Efeito Epidemiológico , Genes Modificadores , Estudos de Associação Genética , Variação Genética/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/fisiologia , Estudos Prospectivos , Neoplasias da Próstata/sangue , Neoplasias da Próstata/genética , Fatores de Risco , Estudos Soroepidemiológicos , Receptor 4 Toll-Like/fisiologia , Tricomoníase/sangue , Tricomoníase/imunologia , Trichomonas vaginalis/imunologia , Trichomonas vaginalis/fisiologiaRESUMO
Mammalian secreted protein acidic and rich in cysteine (SPARC) is the primary regulator of cell shape and cell adhesion to fibronectin. We, for the first time, report the complete sequencing of SPARC cDNA from orange-spotted grouper. Despite the difference in the lengths of the SPARC transcripts, all of the SPARC molecules encoded a signal peptide, follistain-like copper binding sequence (KGHK) domain, and extracellular domain. The grouper SPARC gene was differentially expressed in vivo and contributed differently to high-level expression of SPARC in muscle. Immunohistochemical staining demonstrated a decreased level of SPARC in nodavirus-infected grouper compared with healthy grouper. Comparative real-time polymerase chain reaction analyses of eye tissues of viral nervous necrosis grouper and healthy grouper were performed. Recombinant SPARC produced changes in grouper cell shape 24 h after treatment. The results provide new insight into the pathogenesis of nodavirus, and demonstrate an experimental rationale for SPARC characterization in nodavirus-infected grouper.
Assuntos
Bass/imunologia , Doenças dos Peixes/imunologia , Nodaviridae , Osteonectina/imunologia , Infecções por Vírus de RNA/imunologia , Sequência de Aminoácidos , Animais , Sequência de Bases , Bass/genética , Clonagem Molecular , DNA Complementar/genética , DNA Complementar/imunologia , Proteínas de Peixes/química , Proteínas de Peixes/genética , Proteínas de Peixes/imunologia , Regulação da Expressão Gênica , Dados de Sequência Molecular , Osteonectina/química , Osteonectina/genética , Infecções por Vírus de RNA/veterinária , Alinhamento de SequênciaRESUMO
BACKGROUND: Anterior mediastinal tumors in pediatric patients may cause severe cardiorespiratory compromise and sudden collapse, especially when anesthesia or analgesic is required. METHOD: We report a 15-year-old boy with a huge anterior mediastinal tumor that caused complete obliteration of right pulmonary artery and left bronchus, that is, complete ventilation-perfusion mismatch. Cardiopulmonary collapse happened after meperidine injection, and extracorporeal membrane oxygenation (ECMO) was instituted. RESULTS: We then put bronchial stents to restore airway patency and proceeded chemotherapy under ECMO support. Extracorporeal membrane oxygenation was removed 40 hours later. However, the patient died of neutropenic sepsis 9 days after admission. CONCLUSIONS: We emphasized the devastating consequences of anterior mediastinal tumor compression on the pulmonary artery and the contralateral-side bronchus and the use of ECMO as a rescue.
Assuntos
Obstrução das Vias Respiratórias/etiologia , Arteriopatias Oclusivas/etiologia , Oxigenação por Membrana Extracorpórea , Parada Cardíaca/etiologia , Parada Cardíaca/terapia , Neoplasias do Mediastino/complicações , Adjuvantes Anestésicos/administração & dosagem , Adjuvantes Anestésicos/efeitos adversos , Adolescente , Arteriopatias Oclusivas/terapia , Brônquios/cirurgia , Humanos , Masculino , Meperidina/administração & dosagem , Meperidina/efeitos adversos , Artéria Pulmonar/diagnóstico por imagem , Radiografia , StentsRESUMO
Although pancreatoblastoma (PB) is an extremely rare tumor, it is the most common pancreatic tumor in children. We reported 2 cases of PB treated at a medical center in Taiwan. One was a 3.5-year-old boy who presented with abdominal pain. Physical examination demonstrated abdominal masses. Multiple pancreatic and hepatic masses were noted by magnetic resonance imaging. He underwent surgical resection but tumor could not be removed completely, which was confirmed by the pathology. He received chemotherapy consisting of cisplatin and doxorubicin after the surgery but the tumor progressed rapidly. He died of progressive disease and sepsis. The other case was a 4-year-old boy presented with abdominal pain. Computed tomography showed pancreatic tumor. He underwent surgical resection and pathology showed PB. He received chemotherapy after complete tumor resection. He is disease free till now. Complete tumor resection is the major difference of these 2 patients and is the most important factor affecting the outcome.
Assuntos
Neoplasias Hepáticas/patologia , Neoplasias Pancreáticas/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Pré-Escolar , Cisplatino/administração & dosagem , Doxorrubicina/administração & dosagem , Evolução Fatal , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/cirurgia , Masculino , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/cirurgia , Taiwan , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
Environmental tobacco smoke (ETS) exposure might increase the risk for childhood asthma, and we hypothesized the effect may be modified by the phase II genes NAD(P)H: quinone oxidoreductase 1 (NQO1) and glutathione S-transferase (GST) M1. To investigate the genetic and environmental associations with asthma, GSTM1 and NQO1 functional polymorphisms and ETS were analyzed in a two-staged cross-sectional study among elementary schoolchildren in Taiwan. Multiple logistic regression analysis revealed a significant association between the Ser allele of the NQO1 Pro187Ser polymorphism and asthma (OR=1.6, 95% CI 1.3-1.8). Although GSTM1 genotype itself was not significantly associated with asthma (OR=1.0, 95% CI 0.8-1.1), the GSTM1 genotype modified the association between the NQO1 polymorphism and asthma in children exposed to ETS (p=0.0002). The NQO1 gene might be involved in the development of asthma, especially in children carrying the GSTM1 null genotype who are exposed to ETS.
Assuntos
Asma/induzido quimicamente , Predisposição Genética para Doença , Glutationa Transferase/genética , NAD(P)H Desidrogenase (Quinona)/genética , Poluição por Fumaça de Tabaco , Asma/genética , Criança , Feminino , Humanos , Masculino , Polimorfismo Genético , Fatores de RiscoRESUMO
Bronchial epithelial cells exposed to allergens typically secrete chemokines to recruit eosinophils. Persistent inflammation and repair responses result in airway remodeling and irreversible airflow limitation. House dust mite (HDM) is a common allergen causing allergic disorders. Thioredoxin (TRX) is a redox protein that scavenges reactive oxygen species (ROS). This study was to elucidate how TRX mediates gene expression of remodeling factors of human bronchial epithelial cells in response to HDM stimuli interacting with eosinophils. This study cultured normal human bronchial epithelial (BEAS-2B) cells with eosinophils exposed to 0.5 microg/ml recombinant Dermatophagoides pteronyssinus 1 (rDer p1) protease to mimic the allergen-immune reaction. Eosinophils were induced by rDer p1 protease to secrete tumor necrosis factor (TNF)-alpha and generate ROS. When cultured with rDer p1-stimulated eosinophils, BEAS-2B cells released interleukin-6 and underwent apoptosis. The HDM-stimulated eosinophils applied oxidative stress and apoptosis to BEAS-2B cells through the release of mediators. Damaged BEAS-2B cells interfered with gene expression of remodeling factors, such as transforming growth factor (TGF)-beta 1, epidermal growth factor receptor (EGFR), cyclin dependent kinase inhibitor (p21(waf)) and matrix metalloproteinase (MMP) 9, relevant to inflammatory response and epithelial repair in airway remodeling. Notably, BEAS-2B cells over-expressing TRX reduced eosinophil-derived apoptosis and suppressed underlying airway remodeling via attenuation of TGF-beta1, EGFR and p21(waf) and up-regulation of MMP9 expression. Results of this study indicated TRX-over-expressing bronchial epithelial cells attenuated TGF-beta1 and activated MMP9 expression to prevent airway remodeling from HDM-induced inflammation. The finding can be as a reference for further therapeutic studies of TRX.