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1.
Adv Exp Med Biol ; 1232: 85-90, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31893398

RESUMO

Delayed orthostatic hypotension (OH) is a minor subset of orthostatic dysregulation (OD). Cerebral blood oxygenation in juvenile patients with delayed OH has not been studied. We investigated the bilateral changes in cerebral oxygenation in the prefrontal cortex during an active standing test in 23 juvenile patients with delayed OH using near-infrared spectroscopy (NIRS). We measured the oxy-Hb, deoxy-Hb, and total-Hb during the active standing test. Four observations were made during the test: t1 in a resting supine position, t2 when maintaining blood pressure, and the remaining two (t3, t4) during hypotension. The concentration of oxy-Hb significantly decreased prior to satisfying the diagnostic criteria of delayed OH after standing and did not change thereafter. The concentration of deoxy-Hb increased gradually during the measurement periods. In addition, total-Hb increased from t2 to t3. There was no significant difference in the change in each Hb parameter between the left and right cerebral hemispheres. Our results indicate that NIRS parameters are more sensitive than blood pressure for the interpretation of cerebral autoregulation in juvenile patients with delayed OH.


Assuntos
Sistema Cardiovascular , Circulação Cerebrovascular , Hipotensão Ortostática , Oxigênio , Posição Ortostática , Adolescente , Pressão Sanguínea , Circulação Cerebrovascular/fisiologia , Humanos , Hipotensão Ortostática/sangue , Hipotensão Ortostática/diagnóstico , Oxigênio/sangue , Espectroscopia de Luz Próxima ao Infravermelho
2.
Lung ; 197(5): 559-564, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31297601

RESUMO

INTRODUCTION: Several studies have reported that single nucleotide polymorphisms (SNPs) in the gene encoding NF-E2-related factor 2 (Nrf2) contribute to airflow limitations in smokers without COPD. Although small airway lesions and emphysema contribute cooperatively to airflow limitation, the relationship between Nrf2 SNPs and the development of emphysema in smokers without COPD is not well understood. METHODS: Healthy subjects who underwent an annual health checkup with computed tomography (CT) of the chest at Osaka City University Hospital were prospectively recruited. The percentage of low-attenuation area (%LAA) on chest CT was quantified, and correlations between %LAA, Nrf2 SNP [rs6726395 (G/A)] genotypes, and clinical characteristics were examined. RESULTS: A total of 245 subjects without COPD [non-/light-smoker: 153 (62.4%) and smoker: 92 (37.6%)] were enrolled. The %LAA in the upper lung field was higher than that in the lower lung field (p < 0.001). The %LAA in smokers was significantly higher than that in non-/light-smokers (p = 0.021). The %LAA showed significant but weak correlation with age in all subjects (r = 0.141, p = 0.028). Divided by genotype, the %LAA of the upper lung field was significantly correlated with age in smokers with genotype GG (wild type) (r = 0.333, p = 0.022), but was not significantly correlated with age in smokers with genotype AG/AA. These correlations were not observed in non-/light smokers. CONCLUSION: A polymorphism rs6726395 in Nrf2 can contribute to the development of emphysema-associated aging in smokers. The Nrf2 SNP may be a predictive factor for smoking-induced emphysema, and genotyping of Nrf2 SNP may serve as biomarker for emphysema prevention.

3.
Phys Rev Lett ; 122(1): 017202, 2019 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-31012682

RESUMO

We studied the magnetic ordering of thin films and bulk crystals of rutile RuO_{2} using resonant x-ray scattering across the Ru L_{2} absorption edge. Combining polarization analysis and azimuthal angle dependence of the magnetic Bragg signal, we have established the presence and characteristic of collinear antiferromagnetism in RuO_{2} with T_{N}>300 K. In addition to revealing a spin-ordered ground state in the simplest ruthenium oxide compound, the persistence of magnetic order even in nanometer-thick films lays the ground for potential applications of RuO_{2} in antiferromagnetic spintronics.

4.
Sci Rep ; 8(1): 2748, 2018 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-29426871

RESUMO

Chlorine resistant reverse osmosis (RO) membranes were fabricated using a multi-walled carbon nanotube-polyamide (MWCNT-PA) nanocomposite. The separation performance of these membranes after chlorine exposure (4800 ppm·h) remained unchanged (99.9%) but was drastically reduced to 82% in the absence of MWCNT. It was observed that the surface roughness of the membranes changed significantly by adding MWCNT. Moreover, membranes containing MWCNT fractions above 12.5 wt.% clearly improved degradation resistance against chlorine exposure, with an increase in water flux while maintaining salt rejection performance. Molecular dynamics and quantum chemical calculations were performed in order to understand the high chemical stability of the MWCNT-PA nanocomposite membranes, and revealed that high activation energies are required for the chlorination of PA. The results presented here confirm the unique potential of carbon nanomaterials embedded in polymeric composite membranes for efficient RO water desalination technologies.

5.
Phys Rev Lett ; 117(13): 135501, 2016 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-27715090

RESUMO

Despite the fact that phase-change materials are widely used for data storage, no consensus exists on the unique mechanism of their ultrafast phase change and its accompanied large and rapid optical change. By using the pump-probe observation method combining a femtosecond optical laser and an x-ray free-electron laser, we substantiate experimentally that, in both GeTe and Ge_{2}Sb_{2}Te_{5} crystals, rattling motion of mainly Ge atoms takes place with keeping the off-center position just after femtosecond-optical-laser irradiation, which eventually leads to a higher symmetry or disordered state. This very initial rattling motion in the undistorted lattice can be related to instantaneous optical change due to the loss of resonant bonding that characterizes GeTe-based phase change materials. Based on the amorphous structure derived by first-principles molecular dynamics simulation, we infer a plausible ultrafast amorphization mechanism via nonmelting.

7.
Ann Oncol ; 27(6): 1143-8, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27069012

RESUMO

BACKGROUND: Peripheral sensory neuropathy (PSN) is a dose-limiting toxicity of oxaliplatin-based chemotherapy. Several genetic markers have been shown to predict oxaliplatin-induced PSN; however, results remain to be validated in a large-scale and prospective pharmacogenomics study. PATIENTS AND METHODS: Among 882 patients enrolled in the JFMC41-1001-C2 (JOIN trial), which was designed to investigate the tolerability of adjuvant-modified FOLFOX6 (mFOLFOX6) in Japanese Patients with stage II or III colon cancers undergoing curative resection, 465 patients were eligible for this pharmacogenomics analysis. Twelve single-nucleotide polymorphisms (SNPs) were selected based on published data. The effect of each genotype on time to PSN onset was evaluated in all patients (n = 465) using the Cox proportional hazard model. For the association analysis between severity of PSN and 12 SNP markers, 84 patients who failed to complete 12 cycles of mFOLFOX6 from grade 0/1 PSN group were excluded because the termination of the protocol treatment had been caused by reasons other than PSN. RESULTS: Comparison of grade 0/1 PSN with grade 2/3 PSN or grade 3 PSN showed no significant associations with any of the 12 SNP markers after adjustment for total dose of oxaliplatin. Time-to-onset analysis also failed to reveal any significant differences. CONCLUSIONS: Our large-scale and prospective pharmacogenomics study of Japanese patients receiving protocol treatment of adjuvant mFOLFOX6 could not verify a role for any of the 12 SNP markers reported as being significantly associated with PSN. Considering the OR observed in this study (range: 0.76-1.89), further evaluation of these 12 SNP markers in the context of L-OHP-induced PSN is unlikely to be clinically informative.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias do Colo/tratamento farmacológico , Doenças do Sistema Nervoso Periférico/genética , Farmacogenética , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimioterapia Adjuvante/efeitos adversos , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Feminino , Fluoruracila/efeitos adversos , Humanos , Japão , Leucovorina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Oxaliplatina , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/patologia , Polimorfismo de Nucleotídeo Único/genética
9.
Cancer Chemother Pharmacol ; 75(6): 1183-9, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25862350

RESUMO

PURPOSE: Capecitabine and S-1 are orally administered fluorinated pyrimidines with high-level activity against metastatic breast cancer (MBC). This randomized, multicenter, phase II study compared the activities and safeties of the oral fluoropyrimidines, capecitabine and S-1, in breast cancer patients. METHODS: Patients with MBC were randomly assigned to receive capecitabine 825 g/m(2) twice daily on days 1-21 every 4 weeks or S-1 40-60 mg twice daily, according to body surface area, on days 1-28 every 6 weeks. The primary endpoint was progression-free survival (PFS). RESULTS: A total of 142 patients were enrolled and randomized to either capecitabine (N = 73) or S-1 (N = 69). Median PFS (progression-free survival) was 1.2 years for capecitabine and 1.3 years for S-1, with a hazard ratio (S-1/capecitabine) of 0.85 (95 % confidence interval [CI] 0.52-1.38) (P = 0.48 by log-rank). The confirmed objective response rates were 24.0 % for capecitabine and 23.1 % for S-1 (P = 0.938). The most common treatment-related adverse events were grade 1-2 in intensity. Thrombocytopenia (S-1: 9.2 %, capecitabine: 1.4 %; P = 0.040) and nausea (S-1: 26.2 %, capecitabine: 14.1 %; P = 0.079) were more frequent in the S-1 group, while hand-foot syndrome occurred more often in the capecitabine group (S-1: 10.8 %, capecitabine: 25.4 %; P = 0.029). CONCLUSIONS: The results of the current study demonstrate that both S-1 and capecitabine are effective and well-tolerated treatments in patients with MBC, while their adverse events were different. They are both convenient, orally administered drugs, making them attractive agents for use in outpatient treatment.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Desoxicitidina/análogos & derivados , Fluoruracila/análogos & derivados , Recidiva Local de Neoplasia/tratamento farmacológico , Ácido Oxônico/uso terapêutico , Pirimidinas/uso terapêutico , Tegafur/uso terapêutico , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/mortalidade , Capecitabina , Desoxicitidina/efeitos adversos , Desoxicitidina/uso terapêutico , Intervalo Livre de Doença , Combinação de Medicamentos , Feminino , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Humanos , Japão , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Pirimidinas/efeitos adversos
10.
Appl Microbiol Biotechnol ; 99(11): 4743-53, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25620369

RESUMO

A maltotriose-forming amylase (G3Amy) from Kitasatospora sp. MK-1785 was successfully isolated from a soil sample by inhibiting typical extracellular α-amylases using a proteinaceous α-amylase inhibitor. G3Amy was purified from the MK-1785 culture supernatant and characterized. G3Amy produced maltotriose as the principal product from starch and was categorized as an exo-α-amylase. G3Amy could also transfer maltotriose to phenolic and alcoholic compounds. Therefore, G3Amy can be useful for not only maltotriose manufacture but also maltooligosaccharide-glycoside synthesis. Further, the G3Amy gene was cloned and expressed in Escherichia coli cells. Analysis of its deduced amino acid sequence revealed that G3Amy consisted of an N-terminal GH13 catalytic domain and two C-terminal repeat starch-binding domains belonging to CBM20. It is suggested that natural G3Amy was subjected to proteolysis at N-terminal region of the anterior CBM20 in the C-terminal region. As with natural G3Amy, recombinant G3Amy could produce and transfer maltotriose from starch.


Assuntos
Amilases/genética , Amilases/metabolismo , Streptomycetaceae/enzimologia , Streptomycetaceae/genética , Trissacarídeos/metabolismo , Clonagem Molecular , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Ribossômico/química , DNA Ribossômico/genética , Escherichia coli/enzimologia , Escherichia coli/genética , Expressão Gênica , Hidrólise , Dados de Sequência Molecular , Estrutura Terciária de Proteína , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Microbiologia do Solo , Amido/metabolismo , Streptomycetaceae/classificação , Streptomycetaceae/isolamento & purificação
11.
Br J Cancer ; 112(2): 357-64, 2015 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-25321194

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/genética
12.
J Synchrotron Radiat ; 21(Pt 6): 1247-51, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25343791

RESUMO

The diffraction anomalous fine structure (DAFS) method that is a spectroscopic analysis combined with resonant X-ray diffraction enables the determination of the valence state and local structure of a selected element at a specific crystalline site and/or phase. This method has been improved by using a polycrystalline sample, channel-cut monochromator optics with an undulator synchrotron radiation source, an area detector and direct determination of resonant terms with a logarithmic dispersion relation. This study makes the DAFS method more convenient and saves a large amount of measurement time in comparison with the conventional DAFS method with a single crystal. The improved DAFS method has been applied to some model samples, Ni foil and Fe3O4 powder, to demonstrate the validity of the measurement and the analysis of the present DAFS method.

13.
Br J Cancer ; 111(8): 1614-24, 2014 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-25117812

RESUMO

BACKGROUND: Recent studies have demonstrated that microRNAs are stably detectable in plasma/serum because of their binding to specific proteins or being packaged in secretory particles. This study was designed to detect novel microRNAs in plasma for cancer detection and monitoring using microRNA array-based approaches in oesophageal squamous cell carcinoma (ESCC) patients. METHODS: Through the integration of two Toray 3D-Gene microRNA array-based approaches to compare plasma microRNA levels between ESCC patients and healthy volunteers and between preoperative and postoperative ESCC patients, we identified a novel plasma biomarker in ESCC. RESULTS: (1) Eight upregulated and common microRNAs (miR-15b, 16, 17, 25, 19b, 20a, 20b, and 106a) were selected using two high-resolution microRNA array approaches. (2) Test-scale analyses by quantitative RT-PCR validated a significant higher levels of plasma miR-19b (P=0.0020) and miR-25 (P=0.0030) in ESCC patients than controls. However, a significant correlation was observed between plasma miR-19b levels and concentrations of red blood cells (P=0.0073) and haemoglobin (P=0.0072). (3) miR-25 expression was found to be significantly higher in ESCC tissues (P=0.0157) and ESCC cell lines (P=0.0093) than in normal tissues and fibroblasts. (4) In a large-scale validation analysis, plasma miR-25 levels were significantly higher in 105 preoperative (P<0.0001) ESCC patients who underwent curative oesophagectomy and 20 superficial ESCC patients who underwent endoscopic resection (P<0.0001) than in 50 healthy volunteers. (5) Plasma miR-25 levels were significantly reduced in postoperative samples than in preoperative samples (P<0.0005) and were significantly increased during ESCC recurrences (P=0.0145). CONCLUSIONS: Plasma miR-25 might be a clinically useful biomarker for cancer detection and the monitoring of tumour dynamics in ESCC patients.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma de Células Escamosas/diagnóstico , Neoplasias Esofágicas/diagnóstico , MicroRNAs/sangue , Idoso , Carcinoma de Células Escamosas/sangue , Neoplasias Esofágicas/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos
14.
Transplant Proc ; 46(2): 651-3, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24656037

RESUMO

Common iliac artery stenosis after renal transplantation is a rare complication; it can occur in the course of hypertension and renal dysfunction. We report a case of suspected renal allograft rejection with iliac artery stenosis proximal to a transplanted kidney. A 52-year-old man with a history of cadaveric kidney transplantation 26 years previously underwent a second cadaveric kidney transplantation in the left iliac fossa because of graft failure 3 years before. In June 2012, the patient had progressive renal dysfunction. In July, a percutaneous needle biopsy was taken, and it showed no rejection; however, his renal function continued to get worse through September. A percutaneous allograft renal biopsy was performed under ultrasound guidance and showed hyperplasia of the juxtaglomerular apparatus and renin granules. Magnetic resonance angiography was used to evaluate the arteries in the pelvis and showed left common iliac artery stenosis, and a stent was placed. After percutaneous intervention, the patient's ankle brachial pressure index was within the normal range and the allograft function had improved.


Assuntos
Biópsia , Constrição Patológica/diagnóstico , Transplante de Rim , Rim/patologia , Artéria Renal/patologia , Adulto , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
15.
J Dent Res ; 92(10): 905-10, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23962749

RESUMO

Hypoxia enhances the reprogramming efficiency of human dermal fibroblasts to become induced pluripotent stem cells (iPSCs). Because we showed previously that hypoxia facilitates the isolation and maintenance of human dental pulp cells (DPCs), we examined here whether it promotes the reprogramming of DPCs to become iPSCs. Unlike dermal fibroblasts, early and transient hypoxia (3% O2) induced the transition of DPCs to iPSCs by 3.3- to 5.1-fold compared with normoxia (21% O2). The resulting iPSCs closely resembled embryonic stem cells as well as iPSCs generated in normoxia, as judged by morphology and expression of stem cell markers. However, sustained hypoxia strongly inhibited the appearance of iPSC colonies and altered their morphology, and anti-oxidants failed to suppress this effect. Transient hypoxia increased the expression levels of NANOG and CDH1 and modulated the expression of numerous genes, including those encoding chemokines and their receptors. Therefore, we conclude that hypoxia, when optimized for cell type, is a simple and useful tool to enhance the reprogramming of somatic cells to become iPSCs.


Assuntos
Caderinas/genética , Hipóxia Celular/genética , Polpa Dentária/citologia , Proteínas de Homeodomínio/genética , Células-Tronco Pluripotentes Induzidas , Animais , Antígenos CD , Antioxidantes/farmacologia , Caderinas/biossíntese , Células Cultivadas , Reprogramação Celular , Proteínas de Homeodomínio/biossíntese , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Proteína Homeobox Nanog , Odontoblastos/citologia , Análise de Sequência com Séries de Oligonucleotídeos/métodos
16.
Br J Cancer ; 108(9): 1822-9, 2013 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-23579215

RESUMO

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 ROC
17.
Br J Cancer ; 108(6): 1324-31, 2013 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-23422756

RESUMO

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 Cultivadas
18.
Br J Cancer ; 108(2): 361-9, 2013 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-23329235

RESUMO

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 , Masculino
19.
Ann Oncol ; 24(4): 980-5, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23136232

RESUMO

BACKGROUND: This study was designed to determine the recommended dose of carboplatin-pemetrexed in elderly (≥75 years old), chemotherapy-naive patients with advanced nonsquamous nonsmall-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients received escalated doses of carboplatin and pemetrexed every 3 weeks for four cycles. Patients with an objective response and stable disease continued pemetrexed therapy until disease progression or unacceptable toxicity was observed. RESULTS: The combination of carboplatin at an area under the concentration-time curve (AUC) of 5, and 500 mg/m(2) pemetrexed, was determined to be the recommended dose for elderly patients with advanced nonsquamous NSCLC. Of 17 patients, 10 received a median of five cycles of pemetrexed maintenance therapy without unexpected or cumulative toxic effects. The study had an overall response rate of 47.1%. The median progression-free survival time was 142 days (95% confidence interval [CI] 68-216 days) and the median overall survival time was 461 days (95% CI 168-754 days). CONCLUSIONS: This combination was a tolerable and effective regimen, and recommended dose (RD) was carboplatin [area under the curve (AUC) of 5]/pemetrexed (500 mg/m(2)) every 3 weeks, in chemotherapy-naïve, elderly (≥75 years old) patients with advanced nonsquamous NSCLC.


Assuntos
Carboplatina/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Glutamatos/administração & dosagem , Guanina/análogos & derivados , Neoplasias Pulmonares/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Área Sob a Curva , Carboplatina/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/patologia , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Glutamatos/efeitos adversos , Guanina/administração & dosagem , Guanina/efeitos adversos , Humanos , Neoplasias Pulmonares/patologia , Masculino , Estadiamento de Neoplasias , Pemetrexede , Taxa de Sobrevida
20.
Transpl Infect Dis ; 15(2): E54-7, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23173742

RESUMO

Severe hyponatremia is a critical electrolyte abnormality in allogeneic stem cell transplantation (allo-SCT) recipients and >50% of cases of severe hyponatremia are caused by the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Here, we present a patient with rapidly progressive severe hyponatremia as an initial sign and symptom of human herpesvirus-6-associated post-transplantation acute limbic encephalitis (HHV-6 PALE) after allo-SCT. A 45-year-old woman with acute lymphoblastic leukemia received unrelated bone marrow transplantation from a one locus-mismatched donor at the DR locus. On day 21, she developed a generalized seizure and loss of consciousness with severe hyponatremia, elevated serum antidiuretic hormone (ADH), and decreased serum osmolality. A high titer of HHV-6 DNA was detected in cerebrospinal fluid. Treatment with foscarnet sodium and hypertonic saline was started with improvement of neurological condition within several days. Although an elevated serum ADH, low serum osmolality, and high urinary osmolality persisted for 2 months, she had no other recurrent symptoms of encephalitis. Our experience suggests that hyponatremia accompanied by SIADH should be recognized as a prodromal or concomitant manifestation of HHV-6 PALE, and close monitoring of serum sodium levels in high-risk patients for HHV-6 PALE is necessary for immediate diagnosis and treatment initiation.


Assuntos
Antivirais/uso terapêutico , Transplante de Medula Óssea , Herpesvirus Humano 6/isolamento & purificação , Hiponatremia/diagnóstico , Síndrome de Secreção Inadequada de HAD/diagnóstico , Encefalite Límbica/diagnóstico , Infecções por Roseolovirus/diagnóstico , DNA Viral/líquido cefalorraquidiano , Diagnóstico Diferencial , Feminino , Foscarnet/uso terapêutico , Herpesvirus Humano 6/genética , Humanos , Hiponatremia/etiologia , Hiponatremia/terapia , Síndrome de Secreção Inadequada de HAD/complicações , Síndrome de Secreção Inadequada de HAD/terapia , Encefalite Límbica/tratamento farmacológico , Encefalite Límbica/virologia , Imagem por Ressonância Magnética , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Infecções por Roseolovirus/tratamento farmacológico , Infecções por Roseolovirus/virologia , Solução Salina Hipertônica/uso terapêutico , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X
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