RESUMO
BACKGROUND: SET and MYND domain-containing protein 2 (SMYD2) is a lysine methyltransferase for histone H3, p53 and Rb and inhibits their transactivation activities. In this study, we tested whether SMYD2 (1q42) acts as a cancer-promoting factor by being overexpressed in gastric cancer. METHODS: We analysed 7 gastric cancer cell lines and 147 primary tumor samples of gastric cancer, which were curatively resected in our hospital. RESULTS: SET and MYND domain-containing protein 2 was detected in these cell lines (five out of seven cell lines; 71.4%) and primary tumor samples (fifty-six out of one hundred and forty-seven cases; 38.1%). Knockdown of SMYD2 using specific small interfering RNA inhibited proliferation, migration and invasion of SMYD2-overexpressing cells in a TP53 mutation-independent manner. Overexpression of SMYD2 protein correlated with larger tumor size, more aggressive lymphatic invasion, deeper tumor invasion and higher rates of lymph node metastasis and recurrence. Patients with SMYD2-overexpressing tumours had a worse overall rate of survival than those with non-expressing tumours (P=0.0073, log-rank test) in an intensity and proportion score-dependent manner. Moreover, multivariate analysis demonstrated that SMYD2 was independently associated with worse outcome (P=0.0021, hazard ratio 4.25 (1.69-10.7)). CONCLUSIONS: These findings suggest that SMYD2 has a crucial role in tumor cell proliferation by its overexpression and highlight its usefulness as a prognostic factor and potential therapeutic target in gastric cancer.
Assuntos
Expressão Gênica , Histona-Lisina N-Metiltransferase/metabolismo , Neoplasias Gástricas/enzimologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Técnicas de Silenciamento de Genes , Histona-Lisina N-Metiltransferase/genética , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/cirurgia , Resultado do Tratamento , Proteína Supressora de Tumor p53/genéticaRESUMO
BACKGROUND: This study investigated the usefulness of a novel inflammation-based prognostic system, named the COP-NLR (COmbination of Platelet count and Neutrophil to Lymphocyte Ratio), for predicting the postoperative survival of patients with colorectal cancer (CRC). METHODS: The COP-NLR was calculated on the basis of data obtained on the day of admission: patients with both an elevated platelet count (>30 × 10(4) mm(-3)) and an elevated NLR (>3) were allocated a score of 2, and patients showing one or neither were allocated a score of 1 or 0, respectively. RESULTS: Four-hundred and eighty patients were enrolled. Multivariate analysis of clinical characteristics selected by univariate analysis showed that the COP-NLR (1, 2/0) (odds ratio, 0.464; 95% confidence interval, 0.267-0.807; P=0.007) had an association with cancer-specific survival, along with pathology, lymph node metastasis, the serum levels of carcinoembryonic antigen, C-reactive protein and albumin, and the Glasgow Prognostic Score. Kaplan-Meier analysis and log-rank test revealed that the COP-NLR was able to divide such patients into three independent groups (P<0.001). CONCLUSION: The COP-NLR is considered to be a useful predictor of postoperative survival in patients with CRC.
Assuntos
Plaquetas/patologia , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/cirurgia , Linfócitos/patologia , Neutrófilos/patologia , Idoso , Idoso de 80 Anos ou mais , Contagem de Células Sanguíneas , Neoplasias Colorretais/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: We recently isolated vasohibin-1 (VASH1), a novel angiogenic molecule that is specifically expressed in activated vascular endothelial cells (ECs), and the status of VASH1 expression has been documented in various cancer angiogenesis. The aim of this study was to assess the prognostic value of VASH1 expression in prostate cancer (PCa). METHODS: In this study, we retrospectively analysed the clinical records and evaluated the VASH1 expression of tumour microvessels in 167 patients with PCa who underwent radical prostatectomy. We immunohistochemically examined the microvessels positive for anti-CD34 as microvessel density (MVD) and the microvessels with activated ECs positive for VASH1 density. RESULTS: We found that the VASH1 expression was restricted to ECs in the tumour stroma. VASH1 density was significantly associated with pathological T stage, Gleason score and MVD. The 5-year PSA recurrence-free survival rate was 58.8% in patients with higher VASH1 density (â§12 per mm(2)) and 89.1% in patients with lower VASH1 density (<12 per mm(2)), respectively (P<0.001). Microvessel density was not an independent predictor of PSA recurrence. Multivariate analysis revealed that high VASH1 density was an independent prognostic indicator of PSA recurrence (P=0.007, HR=2.950). CONCLUSION: VASH1 density represents a clinically relevant predictor of patient prognosis and can be a new biomarker that would provide additional prognostic information in PCa.
Assuntos
Carcinoma/diagnóstico , Proteínas de Ciclo Celular/metabolismo , Neoplasias da Próstata/diagnóstico , Idoso , Biomarcadores Tumorais/metabolismo , Carcinoma/irrigação sanguínea , Carcinoma/metabolismo , Carcinoma/mortalidade , Contagem de Células , Humanos , Masculino , Microvasos/metabolismo , Microvasos/patologia , Pessoa de Meia-Idade , Neovascularização Patológica/diagnóstico , Neovascularização Patológica/metabolismo , Prognóstico , Antígeno Prostático Específico/metabolismo , Neoplasias da Próstata/irrigação sanguínea , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/mortalidade , Estudos Retrospectivos , Análise de SobrevidaRESUMO
BACKGROUND: Several recent studies have demonstrated that microRNAs (miRNAs) are stably detectable in plasma/serum. We tested miR-221 and miR-375, which are frequently reported to be highly and poorly expressed in pancreatic cancer (PCa), as candidates for plasma biomarkers in PCa. METHODS: This study was divided into three parts: (1) Confirmation of higher miR-221 levels in primary PCa tissue and cell lines than normal pancreatic tissues. (2) Evaluation of plasma miR-221 and miR-375 concentrations by comparing results from 47 consecutive PCa patients and 30 healthy volunteers. (3) Evaluation of the assay for monitoring tumour dynamics in PCa patients. RESULTS: (1) Expression of miR-221 was significantly higher in PCa tissues and cell lines than normal pancreatic tissues. (2) Plasma miR-221 concentrations were significantly higher in PCa patients than that in benign pancreatic tumours (P=0.016) and controls (P<0.0005), while plasma miR-375 concentrations tended to be lower in PCa patients (P=0.064), and the miR-221/miR-375 ratio was significantly higher (P<0.0001) in PCa patients than in controls. (3) Plasma miR-221 concentrations were significantly reduced in postoperative samples (P=0.018). Furthermore, PCa patients with high plasma miR-221 concentrations had significant correlation with distant metastasis (P=0.041), and non-resectable status (P=0.021). CONCLUSION: Plasma miR-221 could be a useful biomarker for cancer detection, monitoring tumour dynamics and predicting malignant outcomes in PCa patients, and may contribute to clinical decision making in PCa treatments.
Assuntos
MicroRNAs/sangue , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/genética , Idoso , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , Feminino , Humanos , MasculinoRESUMO
BACKGROUND: Several studies have demonstrated that YWHAZ (14-3-3ζ), included in the 14-3-3 family of proteins, has been implicated in the initiation and progression of cancers. We tested whether YWHAZ acted as a cancer-promoting gene through its activation/overexpression in gastric cancer (GC). METHODS: We analysed 7 GC cell lines and 141 primary tumours, which were curatively resected in our hospital between 2001 and 2003. RESULTS: Overexpression of the YWHAZ protein was frequently detected in GC cell lines (six out of seven lines, 85.7%) and primary tumour samples of GC (72 out of 141 cases, 51%), and significantly correlated with larger tumour size, venous and lymphatic invasion, deeper tumour depth, and higher pathological stage and recurrence rate. Patients with YWHAZ-overexpressing tumours had worse overall survival rates than those with non-expressing tumours in both intensity and proportion expression-dependent manner. YWHAZ positivity was independently associated with a worse outcome in multivariate analysis (P=0.0491, hazard ratio 2.3 (1.003-5.304)). Knockdown of YWHAZ expression using several specific siRNAs inhibited the proliferation, migration, and invasion of YWHAZ-overexpressing GC cells. Higher expression of the YWHAZ protein was significantly associated with the lower expression of miR-375 in primary GC tissues (P=0.0047). CONCLUSION: These findings suggest that YWHAZ has a pivotal role in tumour cell proliferation through its overexpression, and highlight its usefulness as a prognostic factor and potential therapeutic target in GC.
Assuntos
Proteínas 14-3-3/metabolismo , Biomarcadores Tumorais/metabolismo , Proliferação de Células , Recidiva Local de Neoplasia/patologia , Neoplasias Gástricas/patologia , Proteínas 14-3-3/antagonistas & inibidores , Proteínas 14-3-3/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Apoptose , Biomarcadores Tumorais/genética , Western Blotting , Adesão Celular , Movimento Celular , Feminino , Seguimentos , Perfilação da Expressão Gênica , Humanos , Técnicas Imunoenzimáticas , Metástase Linfática , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/metabolismo , Estadiamento de Neoplasias , Análise de Sequência com Séries de Oligonucleotídeos , Prognóstico , RNA Mensageiro/genética , RNA Interferente Pequeno/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Taxa de Sobrevida , Células Tumorais CultivadasRESUMO
BACKGROUND: Several recent studies demonstrated that microRNAs are stably detectable in plasma/serum. We tested whether miR-18a, which is located in the miR-17-92 cluster and reported to be highly expressed in tissues of oesophageal squamous cell carcinoma (ESCC), served as a plasma biomarker in patients with ESCC. METHODS: This study was divided into three steps: (1) confirmation of higher miR-18a levels in primary ESCC tissues and cell lines than normal ESCC tissues and a human fibroblast cell line. (2) Evaluation of the plasma miR-18a assay using quantitative RT-PCR by comparing results from 106 consecutive patients with ESCC and 54 healthy volunteers. (3) Evaluation of the assay for monitoring tumour dynamics in patients with ESCC. RESULTS: (1) Expression of miR-18a was significantly higher in ESCC tissues (P=0.0020) and ESCC cell lines (P=0.0121) than normal tissues and fibroblasts. (2) Plasma concentrations of miR-18a were significantly higher in ESCC patients than healthy volunteers (P<0.0001; ESCC patients vs healthy volunteers (mean±s.d.): 11.77±13.45 vs 0.73±0.54 amol µl(-1)). The value of the area under the receiver-operating characteristic (ROC) curve (AUC) was 0.9449. Furthermore, the ROC curves to detect early ESCC such as pTis-1 and pStage0-I showed AUCs of 0.9479 and 0.9642, respectively. (3) Plasma levels of miR-18a were significantly lower in postoperative samples than preoperative samples (P=0.0076). CONCLUSION: Plasma miR-18a may be a very useful biomarker for cancer detection and the monitoring of tumour dynamics in patients with ESCC.
Assuntos
Biomarcadores Tumorais/sangue , Carcinoma de Células Escamosas/sangue , Neoplasias Esofágicas/sangue , MicroRNAs/sangue , Idoso , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/genética , Linhagem Celular Tumoral , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/genética , Humanos , MicroRNAs/biossíntese , MicroRNAs/genética , Prognóstico , Curva ROCRESUMO
BACKGROUND: Recently, it was reported that plasma microRNAs (miRNAs) are low-invasive useful biomarkers for cancer. We attempted to isolate gastric cancer (GC)-associated miRNAs comparing pre- and post-operative paired plasma, thereby excluding the possible effects of individual variability. METHODS: This study was divided into four steps: (1) microarray analysis comparing pre- and post-operative plasma; (2) validation of candidate miRNAs by quantitative RT-PCR; (3) validation study of selected miRNAs using paired plasma; and (4) comparison of the levels of selected miRNAs in plasma between healthy controls and patients. RESULTS: From the results of microarray analysis, nine candidate miRNAs the levels of which were markedly decreased in post-operative plasma were selected for further studies. After confirmation of their post-operative marked reduction, two candidate miRNAs, miR-451 and miR-486, were selected as plasma biomarkers, considering the abundance in plasma, and marked decrease in post-operative samples. In validation, the two miRNAs were found to decrease in post-operative plasma in 90 and 93% of patients (both P<0.01). In comparison with healthy controls, the levels of both miRNAs were found to be significantly higher in patients, and the area under the curve values were high at 0.96 and 0.92. CONCLUSION: Plasma miR-451 and miR-486 could be useful blood-based biomarkers for screening GC.
Assuntos
MicroRNAs/sangue , Neoplasias Gástricas/genética , Biomarcadores Tumorais/sangue , Detecção Precoce de Câncer , Feminino , Humanos , Masculino , Análise em Microsséries , Período Pós-Operatório , Período Pré-Operatório , Neoplasias Gástricas/sangue , Neoplasias Gástricas/cirurgia , Estudos de Validação como AssuntoRESUMO
BACKGROUND: The purpose of this observational study was to investigate the relationship between splanchnic and renal blood flow during infrarenal aortic cross-clamp (XC) and postoperative gastrointestinal perfusion and function. METHODS: Descending aortic blood flow (DABF) was continuously monitored with an oesophageal Doppler monitor (Cardio-Q, Deltex Ltd, Chichester, UK) in 31 patients undergoing elective abdominal aortic aneurysm repair. Cardiac output (CO) was determined by indocyanine green dilution before, during, and after XC. Perioperative gastrointestinal perfusion was assessed by gastric intramucosal pH (pHi, Tonocap, GE Healthcare, Helsinki, Finland). Postoperative gastrointestinal recovery was assessed by the number of postoperative days until the patient successfully resumed solid food intake. The relationship between the mean DABF during XC and gastric pHi after XC release and postoperative gastrointestinal recovery was analysed with Spearman's correlation coefficient. RESULTS: accounted for â¼ 55% of CO during XC and significantly decreased during XC, despite arterial pressure remaining within an optimal range. There were two distinct relationships between DABF during XC and gastric pHi after XC release. Gastric pHi steeply and linearly declined when indexed DABF was below 0.82 litre min(-1) m(-2). Above this critical value, there was no linear relationship between them. The duration of postoperative gastrointestinal dysfunction was inversely correlated with the mean DABF during XC. The best cut-off value of the mean indexed DABF during XC to prevent prolonged gastrointestinal dysfunction was 1.2 litre min(-1) m(-2). CONCLUSIONS: Decreased DABF during XC associates splanchnic hypoperfusion after XC release and delayed recovery of gastrointestinal function.
Assuntos
Aorta Torácica/fisiopatologia , Aneurisma da Aorta Abdominal/cirurgia , Trato Gastrointestinal/fisiopatologia , Circulação Esplâncnica , Adulto , Idoso , Idoso de 80 Anos ou mais , Aneurisma da Aorta Abdominal/fisiopatologia , Débito Cardíaco , Feminino , Determinação da Acidez Gástrica , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Fluxo Sanguíneo RegionalRESUMO
Abnormal immunological responses to certain microbial agents may play a crucial role in the pathogenesis of Kawasaki disease (KD). The association studies between histo-blood group genes (Lewis and ABO blood types) and various types of infectious diseases or vasculopathy have been carried out based on the fact that glycosylated antigens could directly mediate microbial infections. We attempted to clarify the role of blood type antigens in the development of KD and coronary artery lesions in KD patients. The subjects included 164 KD patients enrolled from 1998 to 2003 (1st group), 232 patients from 2004 to 2009 (2nd group), and 223 healthy children and 118 patients with growth hormone deficiency as controls. The genotyping of the FUT2 and FUT3 genes, and ABO genotypes, was determined with the TaqMan SNP assay and allele-specific polymerase chain reaction. No significant differences were observed in the genotypes and allele frequencies of the FUT2 and FUT3 genes between the groups. The frequency of the BB blood genotype was significantly higher in KD patients with coronary artery lesions in the 1st and 2nd groups than in the controls (17% and 14% vs. 5%, P = 0.0020). This is the first report to investigate the roles of ABO and Lewis blood types in the development of KD, and in the formation of coronary artery lesions in KD patients. These data suggest that the ABO blood type may play a role in the development of coronary artery lesions in KD patients.
Assuntos
Sistema ABO de Grupos Sanguíneos/genética , Doença da Artéria Coronariana/genética , Vasos Coronários/patologia , Predisposição Genética para Doença , Síndrome de Linfonodos Mucocutâneos/sangue , Polimorfismo Genético , Alelos , Estudos de Casos e Controles , Pré-Escolar , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/patologia , Feminino , Fucosiltransferases/genética , Frequência do Gene , Técnicas de Genotipagem , Humanos , Lactente , Antígenos do Grupo Sanguíneo de Lewis/genética , Masculino , Síndrome de Linfonodos Mucocutâneos/genética , Síndrome de Linfonodos Mucocutâneos/patologia , Estações do Ano , Galactosídeo 2-alfa-L-FucosiltransferaseRESUMO
BACKGROUND: Several recent studies have demonstrated that microRNAs (miRNAs) are stably detectable in the plasma/serum. We hypothesised that miR-18a in the plasma is a potential biomarker in patients with pancreatic cancer. METHODS: miR-18a is located in the miR-17-92 cluster and reported to be highly expressed in pancreatic cancer tissues. This study was divided into three parts: (1) Confirmation of higher miR-18a levels in primary pancreatic cancer tissues and cell lines than in normal pancreatic tissues and a human fibroblast cell line. (2) Evaluation of the plasma miR-18a assay using quantitative RT-PCR by comparing plasma results obtained from 36 patients with pancreatic cancer and from 30 healthy volunteers. (3) Evaluation of the assay for monitoring tumour dynamics in patients with pancreatic cancer. RESULTS: (1) The expression of miR-18a was significantly higher in pancreatic cancer tissues (P=0.012) and pancreatic cancer cell lines (P=0.015) than in normal tissues and fibroblasts. (2) Plasma concentrations of miR-18a were significantly higher in pancreatic cancer patients than in controls (P<0.0001). The value of the area under the receiver-operating characteristic curve (AUC) was 0.9369. (3) Plasma levels of miR-18a were significantly lower in postoperative samples than in preoperative samples (P=0.0077). CONCLUSION: Circulating miR-18a might provide new complementary tumour markers for pancreatic cancer.
Assuntos
Biomarcadores Tumorais/sangue , MicroRNAs/sangue , Neoplasias Pancreáticas/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , Criança , Pré-Escolar , Feminino , Fibroblastos/metabolismo , Testes Genéticos/métodos , Humanos , Lactente , Recém-Nascido , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/patologia , Reação em Cadeia da Polimerase em Tempo Real/métodos , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Adulto JovemRESUMO
BACKGROUND: Several recent studies demonstrated that microRNAs (miRNAs) are stably detectable in plasma/serum. We hypothesised that plasma miRNAs concentrations contributed to potential biomarkers in patients with oesophageal squamous cell carcinoma (ESCC). METHODS: We selected three oncogenic miRNAs (miR-21, miR-184, miR-221) and one tumour suppressive miRNA (miR-375), which are frequently reported in squamous cell carcinoma, as candidate targets for this plasma miRNA assay. This study was divided into three steps: (1) Determination of appropriate plasma miRNAs in preliminary tests. (2) Evaluation of whether the plasma miRNA assays could monitor tumour dynamics. (3) Validation study on the clinical application of plasma miRNA assays in 50 ESCC patients and 20 healthy volunteers. RESULTS: (1) In preliminary tests, the plasma level of miR-21 was significantly higher (P=0.0218) and that of miR-375 (P=0.0052) was significantly lower in ESCC patients than controls. (2) The high plasma miR-21 levels reflected tumour levels in all cases (100%). The plasma level of miR-21 was significantly reduced in postoperative samples (P=0.0058). (3) On validation analysis, the plasma level of miR-21 tended to be higher in ESCC patients (P=0.0649), while that of miR-375 was significantly lower (P<0.0001) and the miR-21/miR-375 ratio was significantly higher (P<0.0001) in ESCC patients than in controls. The value of the area under the receiver-operating characteristic curve (AUC) was 0.816 for the miR-21/miR-375 ratio assay. Patients with a high plasma level of miR-21 tended to have greater vascular invasion (P=0.1554) and to show a high correlation with recurrence (P=0.0164). CONCLUSION: Detection of circulating miRNAs might provide new complementary tumour markers for ESCC.
Assuntos
Biomarcadores Tumorais/sangue , Carcinoma de Células Escamosas/sangue , Neoplasias Esofágicas/sangue , MicroRNAs/sangue , Idoso , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/genética , Estudos de Casos e Controles , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/genética , Feminino , Humanos , Metástase Linfática , Masculino , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/genética , Prognóstico , Taxa de SobrevidaRESUMO
BACKGROUND: Surgical resection is the most effective treatment for patients with stage II colorectal cancer (CRC). However, a few patients with early-phase CRC suffer postoperative cancer death. AIMS: To investigate the risk factors for postoperative cancer death in patients who undergo surgery for stage II CRC. METHODS: Prognostic significance was analyzed by χ(2) test, univariate analyses, Kaplan-Meier analysis and log-rank test using clinicopathological factors from the database. RESULTS: A total of 205 patients with stage II CRC were evaluated. Age (≤ 65/>65 years), venous invasion (negative/positive), number of dissected lymph nodes (≤ 9/≥ 10), grade of lymph node dissection (sufficient/insufficient) and albumin level (< 3.5/≥ 3.5 g/dl) were associated with shorter overall survival. Univariate analysis of the clinicopathological factors revealed that only the grade of lymph node dissection (sufficient/insufficient) was associated with postoperative cancer death (odds ratio 2.993, 95% confidence interval 1.216-7.368, p = 0.017).Kaplan-Meier analysis and log-rank test revealed that the group with insufficient lymph node dissection had a higher incidence of postoperative cancer death than the group with sufficient dissection (p < 0.001). CONCLUSIONS: Insufficient lymph node dissection is an independent risk factor for postoperative cancer death in patients who undergo surgery for stage II CRC.
Assuntos
Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/cirurgia , Excisão de Linfonodo , Idoso , Neoplasias Colorretais/sangue , Neoplasias Colorretais/patologia , Feminino , Humanos , Hipoalbuminemia/complicações , Japão/epidemiologia , Estimativa de Kaplan-Meier , Excisão de Linfonodo/efeitos adversos , Excisão de Linfonodo/métodos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Período Pós-Operatório , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Albumina Sérica/metabolismoRESUMO
BACKGROUND AND PURPOSE: The newly developed ultra-high-resolution CT is equipped with a 0.25-mm detector, which has one-half the conventional section thickness, one-half the in-plane detector element width, and one-half the reconstructed pixel width compared with conventional-detector CT. Thus, the ultra-high-resolution CT scanner should provide better image quality for microvasculature than the conventional-detector CT scanners. This study aimed to determine whether ultra-high-resolution CT produces superior-quality images of the lenticulostriate arteries compared with conventional-detector CT. MATERIALS AND METHODS: From February 2017 to June 2017, thirteen patients with aneurysms (4 men, 9 women; mean age, 61.2 years) who underwent head CTA with both ultra-high-resolution CT and conventional-detector CT were enrolled. Two board-certified radiologists determined the number of all lenticulostriate arteries on the CTA coronal images of the MCA M1 segment reconstructed from 512 matrixes on conventional-detector CT and 1024 matrixes on ultra-high-resolution CT. RESULTS: There were statistically more lenticulostriate arteries identified on ultra-high-resolution CT (average, 2.85 ± 0.83; 95% CI, 2.509-3.183) than on conventional-detector CT (average, 2.17 ± 0.76; 95% CI, 1.866-2.480) (P = .009) in 16 of the total 26 MCA M1 segments. CONCLUSIONS: Improvements in lenticulostriate artery visualization were the result of the combined package of the ultra-high-resolution CT scanner plus the ultra-high-resolution scanning protocol, which includes higher radiation doses with lower than the national diagnostic reference levels and stronger adaptive iterative dose-reduction processing. This package for ultra-high-resolution CT is a simple, noninvasive, and easily accessible method to evaluate microvasculature such as the lenticulostriate arteries.
Assuntos
Artérias/diagnóstico por imagem , Encéfalo/irrigação sanguínea , Encéfalo/diagnóstico por imagem , Angiografia por Tomografia Computadorizada/métodos , Neuroimagem/métodos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cintilografia/métodos , Estudos RetrospectivosRESUMO
ICRF-193, a novel noncleavable, complex-stabilizing type topoisomerase (topo) II inhibitor, has been shown to target topo II in mammalian cells (Ishida, R., T. Miki, T. Narita, R. Yui, S. Sato, K. R. Utsumi, K. Tanabe, and T. Andoh. 1991. Cancer Res. 51:4909-4916). With the aim of elucidating the roles of topo II in mammalian cells, we examined the effects of ICRF-193 on the transition through the S phase, when the genome is replicated, and through the M phase, when the replicated genome is condensed and segregated. Replication of the genome did not appear to be affected by the drug because the scheduled synthesis of DNA and activation of cdc2 kinase followed by increase in mitotic index occurred normally, while VP-16, a cleavable, complex-stabilizing type topo II inhibitor, inhibited all these processes. In the M phase, however, late stages of chromosome condensation and segregation were clearly blocked by ICRF-193. Inhibition at the stage of compaction of 300-nm diameter chromatin fibers to 600-nm diameter chromatids was demonstrated using the drug during premature chromosome condensation (PCC) induced in tsBN2 baby hamster kidney cells in early S and G2 phases. In spite of interference with M phase chromosome dynamics, other mitotic events such as activation of cdc2 kinase, spindle apparatus reorganization and disassembly and reassembly of nuclear envelopes occurred, and the cells traversed an unusual M phase termed "absence of chromosome segregation" (ACS)-M phase. Cells then continued through further cell cycle rounds, becoming polyploid and losing viability. This effect of ICRF-193 on the cell cycle was shown to parallel that of inactivation of topo II on the cell cycle of the ts top2 mutant yeast. The results strongly suggest that the essential roles of topo II are confined to the M phase, when the enzyme decatenates intertwined replicated chromosomes. In other phases of the cycle, including the S phase, topo II may thus play a complementary role with topo I in controlling the torsional strain accumulated in various genetic processes.
Assuntos
Ciclo Celular/efeitos dos fármacos , Ciclo Celular/genética , Cromossomos/fisiologia , DNA Topoisomerases Tipo II/fisiologia , Piperazinas/farmacologia , Poliploidia , Animais , Células CHO , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Cromossomos/efeitos dos fármacos , Cricetinae , Dicetopiperazinas , Células HeLa , Humanos , Membrana Nuclear/efeitos dos fármacos , Inibidores da Topoisomerase IIRESUMO
The shortage of organ donors has impeded the development of human hepatocyte transplantation. Immortalized hepatocytes, however, could provide an unlimited supply of transplantable cells. To determine whether immortalized hepatocytes could provide global metabolic support in end-stage liver disease, rat hepatocyte clones were developed by transduction with the gene encoding the simian virus 40 T antigen (SVLT) using the new technique of human artificial mini chromosome (HAC). Immortalized rat hepatocyte clones were developed by transduction with the gene encoding the SV40 using HAC. Many clones were obtained using this technique. From comparison of the properties of all these clones using the normal hepatocytes and reverse transcription-polymerase chain reaction (RT-PCR), the characteristics of the cell clones (at least partially characterized, and assayed for albumin, glucose-6-phosphate and dipeptidyl peptidase-4, gamma-glutamyltranspeptidase, SVLT and beta-actin expression by RT-PCR) showed no differences other than the immortalization. We compared the albumin bands of the first-day (0-day) and 30-day cells by RT-PCR, showing conditions to be stable for at least 1 month. Three experimental animal model groups were used for albumin analysis: nonalbumin rats with 2/3 hepatectomy only (R-NARs; n = 4); R-NARs with intrasplenic transplantation of 3 x 10(7) primary hepatocytes (pHTx; n = 4); and R-NARs with intrasplenic transplantation of 3 x 10(7) immortalized hepatocytes (iHTx; n = 4). All HTx groups produced albumin, but the immortalized hepatocyte group did not generate significantly elevated albumin levels compared with primary hepatocytes. The results presented herein have demonstrated an initial step toward the development of immortalized hepatocytes for transplantable cells or artificial organs using HAC technology.
Assuntos
Cromossomos Artificiais Humanos/genética , Hepatócitos/transplante , Albumina Sérica/genética , Animais , Células CHO , Cromossomos Artificiais Humanos/fisiologia , Cricetinae , Cricetulus , Feminino , Hepatócitos/fisiologia , Humanos , Masculino , Ratos , Ratos Endogâmicos Lew , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
BACKGROUND: The Centers for Disease Control and Prevention guideline recommended the use of 2% chlorhexidine as a percutaneous disinfectant for central venous catheter (CVC) insertion. However, in Japan, 0.05% chlorhexidine is commonly used as well as 10% povidone-iodine, instead of 2% chlorhexidine. PURPOSE: It was the aim of this study to examine whether the use of 0.05% chlorhexidine is inferior to conventional 10% povidone-iodine as a percutaneous disinfectant for preventing CVC-related bloodstream infection (CVC-RBSI). METHODS: Between September 2006 and July 2008, the time interval from insertion to development of CVC-RBSI was compared prospectively between patients prepared with 0.05% chlorhexidine (group 1, n = 286 CVCs) and those prepared with conventional 10% povidone-iodine (group 2, n = 298 CVCs). RESULTS: Two hundred and thirty-nine patients received 584 CVCs for a total of 6,205 catheter-days. CVC-RBSI (3.22 per 1,000 catheter-days) was diagnosed in 20 cases. There were no significant differences in patient background factors between group 1 and 2, except for blood culture positivity (p = 0.0450). However, Kaplan-Meier analysis and the log rank test revealed no significant difference between group 1 and 2 in the time interval from insertion until development of CVC-RBSI. CONCLUSIONS: Use of 0.05% chlorhexidine is not inferior to conventional 10% povidone-iodine as a cutaneous disinfectant for the prevention of CVC-RBSI.
Assuntos
Anti-Infecciosos Locais/uso terapêutico , Infecções Relacionadas a Cateter/prevenção & controle , Cateterismo Venoso Central/efeitos adversos , Clorexidina/uso terapêutico , Povidona-Iodo/uso terapêutico , Idoso , Neoplasias Colorretais/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
In this paper, a submerged membrane bioreactor was used to treat 'higher-load' grey water: (a) kitchen-sink wastewater only, and (b) a mixture of kitchen-sink wastewater and washing-machine wastewater. For each type of wastewater, three systems operated at different hydraulic retention times (HRTs) were investigated. In the mixture of kitchen-sink wastewater and washing-machine wastewater, the reactor with a short HRT of four hours was stopped due to foaming. It has been observed that for both types of wastewater, an HRT of eight hours or longer can be used for the treatment. However, it has been observed that a higher COD in the permeate of the mixture can be obtained compared with that of the kitchen-sink wastewater only. This indicated that washing-machine wastewater has some component that is not easily biodegradable. The total linear akylbenzene sulfonate (LAS) removal was > 99% even at a concentration of 10-23 mg 1(-1).
Assuntos
Reatores Biológicos , Membranas Artificiais , Eliminação de Resíduos Líquidos/métodos , Conservação dos Recursos NaturaisRESUMO
OBJECTIVES: To determine the association between sarcopenia and overactive bladder (OAB) in elderly diabetic patients using the Japanese version of SARC-F called SARC-F-J. DESIGN: Cross-sectional study. SETTINGS AND PARTICIPANTS: The study included 329 elderly diabetic patients (aged ≥65 years) who regularly visited the outpatient clinic at Community hospital in Japan. MEASUREMENTS: The condition of OAB was evaluated using the OAM symptom score, which involves a self-administered questionnaire, and sarcopenia was evaluated using the self-administered SARC-F-J questionnaire comprising five items. The odds ratio for OAB due to sarcopenia was calculated using multiple logistic regression analysis, with OAB as the dependent variable and sarcopenia as the explanatory variable. RESULTS: A total of 329 patients (186 males, 143 females) were included for analysis in the present study. Of these patients, 22.9% had sarcopenia and 18.7% had OAB. After adjusting the variables, the odds ratio for OAB due to sarcopenia was 4.46 (95% confidence interval [CI], 1.14-17.36, P = 0.031) and 2.09 (95% CI, 0.52-8.26, P = 0.293) for males and females, respectively. CONCLUSION: This study found that sarcopenia was significantly associated with OAB in elderly diabetic male patients based on SARC-F-J. Moreover, the possibility of the development of OAB should be considered during the medical examinations of elderly diabetic male patients with sarcopenia.
Assuntos
Complicações do Diabetes/complicações , Sarcopenia/complicações , Bexiga Urinária Hiperativa/etiologia , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Masculino , Inquéritos e QuestionáriosRESUMO
Although islet transplantation has been remarkably improved by the Edmonton protocol, the insulin independence rate after islet transplantation from one donor pancreas has remained low. The c-Jun NH2-terminal kinases (JNKs) are classic stress-activated protein kinases; many cellular stresses have been shown to stimulate JNK activation. JNK in the pancreas is activated during brain death, pancreas procurement, and organ preservation, and its activity is progressively increased during the isolation procedure. Moreover, JNK activity in the transplanted liver after islet transplantation increases markedly within 24 hours. In this study, we show the effect of a JNK inhibitor during islet isolation and transplantation. Use of the JNK inhibitor in pancreas preservation, islet culture, and/or islet transplantation prevents islet cell apoptosis and improves islet graft function. These findings suggest that inhibition of JNK could prevent the impairment of islet cells and improve outcomes after pancreatic islet transplantation.
Assuntos
Inibidores Enzimáticos/uso terapêutico , Transplante das Ilhotas Pancreáticas/fisiologia , Ilhotas Pancreáticas/citologia , MAP Quinase Quinase 4/antagonistas & inibidores , Animais , Glicemia/metabolismo , Separação Celular , Diabetes Mellitus Experimental/cirurgia , Ilhotas Pancreáticas/efeitos dos fármacos , Camundongos , Resultado do TratamentoRESUMO
BACKGROUND: Islet transplantation is gradually gaining acceptance for the treatment of type 1 diabetes mellitus. One of the unknown questions is alcohol intake; we have prohibited alcohol intake after islet transplantation although there is no solid evidence to support this. MATERIALS AND METHODS: In this study, we employed a mouse model to determine the effect of oral ethanol intake on transplanted islets. Either 500 or 150 islets were infused selectively into the right liver lobe of chemically induced diabetic mice. After transplantation, mice were orally administered either water (as a control) or various concentrations of ethanol for 14 consecutive days occasionally (once per day) or continuously (all intake was alcohol). Blood glucose levels were monitored and oral glucose tolerance tests (OGTT) performed. RESULTS: After 500 islets had been transplanted, all mice were cured from diabetes, but the continuous alcohol intake group showed significantly prolonged time to diabetes reversal and significantly lower glucose clearance rates by OGTT compared with the control group. After 150 islet transplantations, the diabetes cure rate in the continuous alcohol intake group was significantly lower than the control group (continuous alcohol vs control: 3/8 vs 11/12, P < .05). However, the occasional alcohol intake group showed no difference from the control group, even with as few as 150 islets transplanted per mouse. CONCLUSION: The present results demonstrated that continuous but not occasional alcohol intake reduced the success of intraportal islet transplantation.