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1.
Int J Clin Oncol ; 2020 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-32533353

RESUMO

OBJECTIVES: To determine risk factors influencing the incidence of parastomal hernia (PH) associated with ileal conduit (IC). METHODS: A total of 194 Japanese patients who underwent IC diversion followed by regular postoperative radiographic follow-up from 2005 through 2016 were enrolled. The diagnosis of PH was determined by computed tomography (CT) for patients with and without related symptoms. The cumulative incidence of PH was assessed by the Kaplan-Meier method. The log-rank test and a multivariate Cox proportional hazards model were used to evaluate risk factors associated with the incidence of PH. RESULTS: PH was observed in 20 patients (10.3%) after a median follow-up of 25.5 months. Of the 20 patients, three were symptomatic. The cumulative incidences were 3.6%, 10.1% and 15.1% at 1, 2 and 5 years after operation, respectively. The median body mass index (BMI) was 23.1 kg/m2 (IQR 20.4-24.6). The BMI and diameter of the passage through the rectus abdominis muscle for the IC (DPRAM) were significant predictors for PH (p = 0.04 and p < 0.001, respectively). In proportional hazards regression analysis, DPRAM ≥ 2.4 cm was the only independent risk factor for developing PH (HR 10.94, 95% CI 3.66-32.64). CONCLUSIONS: The incidence of PH in the current Japanese series was relatively low. Even in the population with low BMI, higher BMI might have an impact on incidence of PH. Moreover, DPRAM was also significantly associated with the incidence, suggesting that the operative procedure for creation of the passage is critical for future development of PH.

2.
Cancer Sci ; 111(7): 2460-2471, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32402135

RESUMO

The present study aimed to evaluate the efficacy of the real-world use of axitinib and to develop a prognostic model for stratifying patients who could derive long-term benefit from axitinib. This was a retrospective, descriptive study evaluating the efficacy of axitinib in patients with metastatic renal cell carcinoma that had been treated with 1 or 2 systemic antiangiogenic therapy regimens at 1 of 36 hospitals belonging to the Japan Urologic Oncology Group between January 2012 and February 2019. The primary outcome was overall survival (OS). Using a split-sample method, candidate variables that exhibited significant relationships with OS were chosen to create a model. The new model was validated using the rest of the cohort. In total, 485 patients were enrolled. The median OS was 34 months in the entire study population, whereas it was not reached, 27 months, and 14 months in the favorable, intermediate, and poor risk groups, respectively, according to the new risk classification model. The following 4 variables were included in the final risk model: the disease stage at diagnosis, number of metastatic sites at the start of axitinib therapy, serum albumin level, and neutrophil : lymphocyte ratio. The adjusted area under the curve values of the new model at 12, 36, and 60 months were 0.77, 0.82, and 0.82, respectively. The efficacy of axitinib in routine practice is comparable or even superior to that reported previously. The patients in the new model's favorable risk group might derive a long-term survival benefit from axitinib treatment.

3.
Int Cancer Conf J ; 8(4): 185-189, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31559120

RESUMO

In this report, we present familial cases of urothelial carcinoma. To investigate the possibility of hereditary urothelial cancer, we performed semiconductor-based next-generation DNA sequencing. A woman in her 80s who had bladder and left ureteral cancer was hospitalized in Sapporo Shirakaba-dai Hospital due to consciousness disturbance. Radiographic evaluation revealed multiple liver metastases and she died 38 days later. Needle necropsy was done for a left ureteral tumor that continued to her bladder tumor and for liver metastases. At the same time, her son in his 60s, who also had muscle-invasive bladder cancer, was admitted to Sapporo Medical University Hospital and underwent neoadjuvant chemotherapy followed by laparoscopic radical cystectomy. DNA was isolated from both cancers and normal controls in each case and analyzed by massive parallel sequencing of 409 cancer-related genes using a targeted, multiplex PCR approach followed by semiconductor sequencing. Somatic mutations of KMT2C and KMT2D were detected in the mother's tumor. Copy number gains of FGFR1, IkBKB, NFkB2, FGFR2, and FLT3 and copy number losses of IGF2R and TP53 were also found in her cancer. In her son's tumor, somatic mutations of FGFR3 and EP300 were identified. Copy number gains of IkBKE/MAPK1/PARP1, EGFR, BRAF, IRS2, MAPK2K1, IGF1R, and ERBB2 and copy number loss of TP53 were also found in his cancer. There were no germline gene mutations related to familial urothelial carcinoma. Although somatic mutation of TP53 was a common feature, these cases with urothelial carcinoma might not be the result of a heredity syndrome.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31094669

RESUMO

In this study, the staphylococcal enterotoxin type A (SEA) contaminant was quantified in cow milk by liquid chromatography-tandem mass spectrometry (LC-MS/MS) with the use of a stable isotope-labelled peptide of SEA as an internal standard. SEA was cleaned up in a two-step process that included pH control and trichloroacetic acid (TCA) precipitation. The pH control phase eliminated other proteins. TCA precipitation cleaned up SEA without special equipment. An appropriate enzyme-to-protein ratio maximised tryptic digestion. A desalting process guaranteed the stable retention of SEA-digested peptides. The coverage of amino-acid sequences (>10%) clearly identified the toxin's presence. SEA was accurately quantified using LC-MS/MS based on a multiple-reaction monitoring mode. The developed method was validated based on spiked recovery tests at 50 and 100 µg kg-1 conducted with two samples collected on a daily basis for five days based on Japanese validation guidelines. The new method exhibited good accuracy which ranged from 80% to 82%. The relative standard deviations of repeatability were 13-14% and the relative standard deviations of within-laboratory reproducibility were 13-18%. These standard deviations satisfied the criteria of the Japanese validation guidelines. The quantification limit was estimated to be 10 µg kg-1.


Assuntos
Enterotoxinas/análise , Contaminação de Alimentos/análise , Leite/química , Peptídeos/química , Animais , Bovinos , Cromatografia Líquida , Marcação por Isótopo , Espectrometria de Massas em Tandem
5.
Urol Oncol ; 37(7): 485-491, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31103335

RESUMO

OBJECTIVE: Our aim was to evaluate the usefulness of serum testosterone to guide treatment decision for castration-resistant prostate cancer (CRPC). METHODS: We conducted a retrospective analysis of 115 patients with CRPC treated with either abiraterone (n = 43) or enzalutamide (n = 72). A serum testosterone level was measured at time of starting of abiraterone or enzalutamide. We determined whether serum testosterone influenced the outcomes of androgen receptor (AR)-targeted therapy. RESULTS: In the very-low testosterone group (<5 ng/dl), the rate of prostate-specific antigen (PSA) response was significantly higher among patients treated with abiraterone compared to enzalutamide (62 vs. 32%, respectively; P = 0.033), with no difference in the low testosterone group (5-<50 ng/dl) (93 vs. 81%, respectively; P = 0.429). During the median follow-up of 26 months, PSA progression-free survival was significantly longer in the low testosterone group than in the very-low testosterone group (12.2 vs. 4.5 months, P<0.001). In the very-low testosterone group, enzalutamide use (HR 3.07, 95% CI 1.36-6.94; P = 0.007), primary androgen deprivation therapy <12 months (HR 2.50, 95% CI 1.23-5.08; P = 0.011) and bone metastases (HR 2.60, 95% CI 1.20-5.64; P = 0.015) were significantly associated with PSA progression. CONCLUSION: Patients with a serum testosterone level ≥5 ng/dl were more likely to receive therapeutic benefits from AR-targeted therapy compared to those with serum testosterone levels <5 ng/dl. However, even for those with a very low serum testosterone level, the efficacy of abiraterone was slightly higher than that of enzalutamide. Therefore, serum testosterone level is a useful biomarker for informing treatment selection for CRPC.

6.
Support Care Cancer ; 27(4): 1491-1496, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30374764

RESUMO

PURPOSE: To evaluate the potential role of levocarnitine supplementation for cancer-related fatigue in patients treated with sunitinib. METHODS: Patients treated with sunitinib for unresectable or metastatic renal cell carcinoma were enrolled prospectively. Assessment of fatigue in each patient was done using the Brief Fatigue Inventory (BFI) questionnaire. Evaluation of fatigue and the serum carnitine level was done at baseline, 2 weeks, and 4 weeks after sunitinib therapy was initiated. All patients were treated with sunitinib 37.5 mg or 50 mg/day orally, with a 4-week administration and 2-week discontinuation schedule. RESULTS: Ten patients were finally enrolled in the study. Seven of them had worsened fatigue at the 2-week assessment and levocarnitine was administrated. All these seven patients whose serum carnitine level at 2 weeks was worse than at the baseline improved after 2-week-L-carnitine supplementation. For six of the seven (85.7%) patients who had L-carnitine supplementation, the BFI score at 4 weeks decreased compared to that at 2 weeks, which indicated improvement of fatigue. CONCLUSIONS: Levocarnitine supplementation for cancer-related fatigue in patients treated with sunitinib appears to have a potential benefit. However, further study with a larger number of patients and longer follow-up is crucial to confirm this.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Carnitina/uso terapêutico , Fadiga/prevenção & controle , Neoplasias Renais/tratamento farmacológico , Sunitinibe/uso terapêutico , Idoso , Antineoplásicos/efeitos adversos , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/psicologia , Suplementos Nutricionais , Fadiga/induzido quimicamente , Feminino , Humanos , Neoplasias Renais/patologia , Neoplasias Renais/psicologia , Masculino , Pessoa de Meia-Idade , Terapias Mente-Corpo , Projetos Piloto , Sunitinibe/efeitos adversos , Inquéritos e Questionários , Resultado do Tratamento
7.
Haematologica ; 104(1): 155-165, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30171029

RESUMO

Epigenetic alterations play an important role in the pathogenesis in multiple myeloma, but their biological and clinical relevance is not fully understood. Here, we show that DOT1L, which catalyzes methylation of histone H3 lysine 79, is required for myeloma cell survival. DOT1L expression levels were higher in monoclonal gammopathy of undetermined significance and smoldering multiple myeloma than in normal plasma cells. Treatment with a DOT1L inhibitor induced cell cycle arrest and apoptosis in myeloma cells, and strongly suppressed cell proliferation in vitro The anti-myeloma effect of DOT1L inhibition was confirmed in a mouse xenograft model. Chromatin immunoprecipitation-sequencing and microarray analysis revealed that DOT1L inhibition downregulated histone H3 lysine 79 dimethylation and expression of IRF4-MYC signaling genes in myeloma cells. In addition, DOT1L inhibition upregulated genes associated with immune responses and interferon signaling. Myeloma cells with histone modifier mutations or lower IRF4/MYC expression were less sensitive to DOT1L inhibition, but with prolonged treatment, anti-proliferative effects were achieved in these cells. Our data suggest that DOT1L plays an essential role in the development of multiple myeloma and that DOT1L inhibition may provide new therapies for myeloma treatment.


Assuntos
Proliferação de Células/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Histona-Lisina N-Metiltransferase/antagonistas & inibidores , Fatores Reguladores de Interferon/metabolismo , Mieloma Múltiplo/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Linhagem Celular Tumoral , Histona-Lisina N-Metiltransferase/genética , Histona-Lisina N-Metiltransferase/metabolismo , Humanos , Fatores Reguladores de Interferon/genética , Camundongos , Camundongos SCID , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/genética , Mieloma Múltiplo/patologia , Proteínas Proto-Oncogênicas c-myc/genética
8.
Artigo em Inglês | MEDLINE | ID: mdl-30475679

RESUMO

In this study, the presence of cereulide in cow's milk was identified and quantified using our validated method with liquid chromatography-tandem mass spectrometry. Cereulide was concentrated using protein acid-precipitation and extracted from the precipitate by using acetonitrile twice. The combination of protein acid-precipitation and extraction sufficiently eliminated the matrix compounds from the milk and a further clean-up step utilising solid-phase extraction could be omitted. For robustly measuring the samples and keeping the MS devices clean, the extraction solution was diluted 10-fold using methanol. Owing to the minimisation of the interferences caused by fragmentation patterns, multiple reaction monitoring information-dependent acquisition-enhanced product ion spectra enabled the characterisation and identification of cereulide. Besides the matrix effect (-4%), an external solvent calibration curve was adapted for accurate quantification. The method was validated using fortified recovery tests, at two concentrations (10 and 50 µg kg-1), using three samples daily on five different days based on the Japanese guidelines. This new method exhibited good accuracy ranging from 91% to 94%. The relative standard deviations of repeatability ranged from 2% to 5%, and the relative standard deviation of within-laboratory reproducibility ranged from 5% to 6%. These standard deviations satisfied the criteria for the Japanese validation guidelines. The limit of quantification (LOQ) was estimated to be 2 µg kg-1. On the product ion spectra at the LOQ level, the library match was satisfactory with a purity fit value of >70%. The method was applied to 14 raw milk and three milk samples pasteurised using the low-temperature, long-time process and collected in Tokyo. None of the samples was found to contain the target toxin.


Assuntos
Depsipeptídeos/análise , Contaminação de Alimentos/análise , Leite/química , Animais , Calibragem , Bovinos , Cromatografia Líquida de Alta Pressão , Espectrometria de Massas em Tandem
9.
Jpn J Clin Oncol ; 48(10): 934-941, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-30169681

RESUMO

Objectives: The aim of this study was to evaluate the efficacy of neoadjuvant gemcitabine and cisplatin (GC) therapy for muscle-invasive bladder cancer (MIBC). Methods: We retrospectively evaluated patients who underwent neoadjuvant GC therapy followed by radical cystectomy from April 2009 through December 2015 in the Sapporo Medical University Urologic Consortium. The efficacy of neoadjuvant chemotherapy (NAC) was assessed based on the pathological T0 (pT0) rate in radical cystectomy specimens, and the recurrence-free survival, cause-specific survival and overall survival (OS) rates. To compare the oncological benefit of NC with GC to that of the methotrexate, vinblastine, adriamycin and cisplatin (MVAC) regimen, we also utilized historical clinical data of patients who were treated with MVAC as NAC followed by radical cystectomy in our institute from 1986 through 2010. Results: Fifty-eight patients receiving neoadjuvant GC therapy and 74 receiving neoadjuvant MVAC were included. The pT0 achieving rates were comparable between the two groups (20.7% vs. 18.9%, P = 0.83). Neoadjuvant GC was associated with a better 2-year OS rate than neoadjuvant MVAC for clinical T2 disease (95.2% vs. 70.8%, P = 0.036). In contrast, in patients with clinical T3 or more advanced disease, neoadjuvant MVAC provided more pT0 (20.0% vs. 5.6%, P = 0.07) and better 2-year OS than neoadjuvant GC (71.1% vs. 55.0%, P = 0.142), although the difference did not reach statistical significance. Conclusions: Neoadjuvant GC had no inferiority in oncological outcomes to MVAC for MIBC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino/uso terapêutico , Desoxicitidina/análogos & derivados , Terapia Neoadjuvante/métodos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Cisplatino/administração & dosagem , Cisplatino/farmacologia , Desoxicitidina/administração & dosagem , Desoxicitidina/farmacologia , Desoxicitidina/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estudos Retrospectivos , Taxa de Sobrevida , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologia , Adulto Jovem
10.
Shokuhin Eiseigaku Zasshi ; 59(4): 183-186, 2018.
Artigo em Japonês | MEDLINE | ID: mdl-30158397

RESUMO

An analytical method for PCBs in fishes using an accelerated solvent extractor (ASE) and GC-MS/MS was evaluated. After the extraction of ASE at 125℃ with n-hexane and clean-up with an AgNO3 silica gel/H2SO4 silica gel multilayer column, samples were analyzed by GC-MS/MS. This method was fast, effective and easy to operate. The limit of quantitation of the method was calculated to be 0.78 µg/kg for total PCBs. The recovery and the coefficient of variation of PCBs (n=5) from 6 fishes (Japanese sea perch, chub mackerel, yellowtail, salmon, pacific saury, and sardine) of total PCBs were 91-108% and 1-3%, respectively.


Assuntos
Peixes , Bifenilos Policlorados/análise , Alimentos Marinhos/análise , Animais , Cromatografia Gasosa-Espectrometria de Massas , Solventes , Espectrometria de Massas em Tandem
11.
Shokuhin Eiseigaku Zasshi ; 59(3): 99-105, 2018.
Artigo em Japonês | MEDLINE | ID: mdl-30033995

RESUMO

A quantitative determination method of erythritol, maltitol, lactitol and trehalose in foods by HPLC, and confirmation method by LC-MS/MS were developed. HPLC analysis was performed on a separation column packed with amino group-binding polymer with acetonitrile-water (80 : 20) as the mobile phase. The column was operated at room temperature, and the three sugar alcohols and trehalose were quantified. LC-MS/MS confirmation was performed on an amino group-bound column with acetonitrile-ammonium acetate solution as the mobile phase, with detection in the SRM mode. At low sample dilution ratios, the analysis may be affected by matrix derived from the sample, but this can be suppressed by 1,000-fold or greater dilution. Recoveries of the three sugar alcohols and trehalose spiked into food samples, such as tea, jelly, tablets (ramune candy), and chocolate, exceeded 90% (CV≦6.1%) in HPLC and 94% (CV≦4.8%) in LC-MS/MS.


Assuntos
Eritritol/análise , Análise de Alimentos/métodos , Maltose/análogos & derivados , Álcoois Açúcares/análise , Trealose/análise , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Maltose/análise , Espectrometria de Massas em Tandem
12.
Oncotarget ; 9(36): 24457-24469, 2018 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-29849953

RESUMO

In this study, we identified microRNAs (miRNAs) involved in cisplatin (CDDP) resistance in bladder cancer (BCa). After establishing CDDP-resistant BCa cell lines (T24RC and EJ138RC), TaqMan arrays revealed that members of the miR-200 family (miR-200b, miR-200a and miR-429) were downregulated in T24RC as compared to parental T24 cells. miR-200b was associated with CDDP sensitivity in BCa cells, and its downregulation was associated with CpG island hypermethylation. Pharmacological demethylation using 5-aza-2'-deoxycytidine restored miR-200b expression, and the combination of 5-aza-2'-deoxycytidine + CDDP strongly inhibited T24RC cell proliferation. Microarray analysis revealed that miR-200b + CDDP induced genes involved in CDDP sensitivity or cytotoxicity, including IGFBP3, ICAM1 and TNFSF10, in the resistant cells. Expression and DNA methylation of miR-200b were inversely associated in primary BCa, and low expression/high methylation was associated with poor overall survival. These results suggest downregulation of miR-200b is associated with CDDP resistance in BCa. Epigenetic silencing of miR-200b may be a marker of CDDP resistance and a useful therapeutic target for overcoming CDDP resistance in BCa.

13.
Jpn J Clin Oncol ; 48(7): 661-666, 2018 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-29733363

RESUMO

Objectives: To clarify the efficacy of intravesical Bacillus Calmette-Guérin (BCG) instillation for non-muscle invasive bladder (NMIBC) cancer with variant histology, especially glandular differentiation or squamous differentiation. Materials and methods: From May 1991 through June 2016, 53 patients were diagnosed retrospectively as having NMIBC with variant histology. Among these patients, 47 NMIBC patients with squamous differentiation or glandular differentiation were analyzed for this study. The median follow-up interval from diagnosis of NMIBC with variant histology was 28.9 months (1.5-168.8). Results: Of these patients, 38 (80.9%) and 9 (19.1%) were diagnosed as having glandular differentiation and squamous differentiation, respectively. Radical cystectomy was conducted for six (12.8%) immediately after the diagnosis of NMIBC with variant histology. Of the 41 patients with bladder preservation, 20 (48.8%), 3 (7.3%), 3 (7.3%) and 15 (36.6%) underwent BCG, THP, MMC and no additional treatment, respectively. There were significant differences between BCG and other treatments or no additional treatment for recurrence (P = 0.034), progression (P = 0.004) and cancer-specific survival (P = 0.014). Conclusion: Overall, our results show that intravesical BCG instillation for variant histology in NMIBC leads to a better prognosis with regard to progression and cause-specific survival than other intravesical treatments or no additional treatment. BCG treatment may also have a clinical benefit for variant histology in non-muscle invasive bladder cancer patients.


Assuntos
Vacina BCG/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Diferenciação Celular , Músculos/patologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Idoso , Idoso de 80 Anos ou mais , Vacina BCG/farmacologia , Diferenciação Celular/efeitos dos fármacos , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Estudos Retrospectivos
14.
Int J Clin Oncol ; 23(4): 734-741, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29442282

RESUMO

PURPOSE: We prospectively evaluated the 90-day postoperative mortality and morbidity of open radical cystectomy by using a standardized reporting methodology. Additionally, we assessed the preoperative characteristics to determine risk factors for major complications. METHODS: This multicenter prospective study included 185 consecutive patients undergoing open radical cystectomy from October 2010 through March 2014. Postoperative complications within 90 days were recorded and graded according to the modified Clavien-Dindo classification. RESULTS: Totally, 328 postoperative complications were observed in 149 patients (80.5%). Of these events, 73 (22.2%) were high grade (≥ Grade III), and developed in 46 patients (24.9%). Three patients (1.6%) died postoperatively. Urinary tract infection, wound complications, and paralytic ileus were common complications that occurred in 55 (29.7%), 42 (22.7%) and 41 (22.2%) patients, respectively. Ureteroenteric stricture was diagnosed in 13 of the 151 patients (8.6%) undergoing intestinal urinary diversion. Emergency room visits were required for 13 patients (7.0%) and readmission after discharge was needed for 36 (19.5%). A body mass index ≥ 25 kg/m2, smoking history and Charlson Comorbidity Index ≥ 2 were independent risk factors for high-grade complications, and their odds ratios (95% confidence intervals) were 2.357 (1.123-4.948), 2.843 (1.225-6.596) and 3.025 (1.390-6.596), respectively. CONCLUSIONS: Open radical cystectomy is associated with a high incidence of postoperative complications. Most, however, are of low grade. Our results suggest that obesity, a smoking history, and increasing comorbidity are risk factors for major complications.


Assuntos
Cistectomia/efeitos adversos , Complicações Pós-Operatórias , Neoplasias da Bexiga Urinária/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Cistectomia/métodos , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Resultado do Tratamento
15.
Urology ; 113: 71-78, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29196070

RESUMO

OBJECTIVE: To clarify the clinical utility of urinary DNA methylation for detection of intravesical recurrence of non-muscle invasive BCa (NMIBC), we performed a 2-center prospective study. PATIENTS AND METHODS: A series of 207 self-voided urine samples were prospectively collected from 132 patients with NMIBC who had undergone transurethral resection of BCa. Methylation of miRNA genes (miR-9-3, miR-124-2, miR-124-3, and miR-137) was analyzed using bisulfite pyrosequencing. The primary end point was detection of intravesical recurrence; the secondary end point was prediction of late recurrence. The number of methylated genes (M-score) or quantitative level of methylation were compared with outcomes. RESULTS: Twenty-six urine specimens were collected on the same day intravesical recurrence was detected, and 14 were collected from patients whose recurrences were found during the subsequent follow-up period (0-632 days, mean, 342.2 days). For detection of current recurrence, M-scores achieved 61.5% sensitivity and 74.0% specificity, and the area under the ROC curve was 0.71. Regarding prediction of late recurrence, patients with a high M-score (≥3) showed worse recurrence-free survival (P <.01). Multivariate analysis revealed that high M-scores were independently associated with current (P = .028) and late recurrence (P = .026). Elevated levels of urinary DNA methylation were also strongly associated with recurrence and radical cystectomy. CONCLUSION: Our data suggest that urinary methylation of miRNA genes may be a useful marker for detecting and predicting BCa recurrence.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma de Células de Transição/genética , MicroRNAs/genética , Recidiva Local de Neoplasia/genética , Neoplasias da Bexiga Urinária/genética , Idoso , Carcinoma de Células de Transição/mortalidade , Carcinoma de Células de Transição/cirurgia , Estudos de Coortes , Metilação de DNA , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , Curva ROC , Medição de Risco , Análise de Sobrevida , Resultado do Tratamento , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/cirurgia
16.
Shokuhin Eiseigaku Zasshi ; 58(5): 221-228, 2017.
Artigo em Japonês | MEDLINE | ID: mdl-29081458

RESUMO

An analytical method based on LC-MS/MS was developed for the determination of formetanate hydrochloride in agricultural products. Formetanate hydrochloride was confirmed to be stable in acetonitrile. It was therefore extracted from samples with acetonitrile, and the crude extracts were purified using a combination of ethylenediamine-N-propyl silylation silica gel and graphite carbon mini columns. Formetanate hydrochloride in the resulting sample solutions was quantified by LC-MS/MS utilizing an external solvent calibration curve. The average recovery (n=5) of formetanate hydrochloride spiked in 10 types of agricultural products (brown rice, soybean, spinach, cabbage, potato, apple, orange, lime, nectarine and green tea) at the maximum residue limits (MRLs) or at a uniform limit of 0.01 mg/kg was 92.3-103%, with a relative standard deviation of 1.3-5.4%. The limit of quantitation of the developed method was calculated to be 0.01 mg/kg.


Assuntos
Carbamatos/análise , Cromatografia Líquida/métodos , Produtos Agrícolas/química , Análise de Alimentos/métodos , Resíduos de Praguicidas/análise , Espectrometria de Massas em Tandem/métodos , Acetonitrilos , Carbamatos/isolamento & purificação , Soluções
18.
Artigo em Inglês | MEDLINE | ID: mdl-28478077

RESUMO

We developed a simultaneous determination method for 37 veterinary drugs in two chicken processed foods (deep-fried chicken and non-fried chicken cutlet) and muscle via liquid chromatography-mass spectrometry. The veterinary drugs belong to 7 different classes, including 4 antifolics, 4 benzimidazoles, 5 macrolides, 7 polyethers, 2 quinolones, 7 sulfonamides, and 8 other classes. The samples were extracted with ethyl acetate followed by acetonitrile with salt and buffers extraction. The two-step extraction enabled analyte extraction from highly lipid samples. The clean-up procedure, a solid-supported liquid extraction clean-up using a diatomaceous earth mini-cartridge, eliminated lipid co-extraction. The prepared sample matrix did not have an effect on the 36 analytes. The method was validated in accordance with the requirements of Japanese validation guidelines. Almost all targeted veterinary drugs successfully satisfied the guideline criteria in the three types of food matrices. The method exhibited recoveries of 70-105%, and the precision of repeatability and within-laboratory reproducibility ranged from 1 to 11% and 1 to 15%, respectively. The limits of quantification were estimated to range from 0.2 to 1.0µg/kg. Applying this method to samples commercially available in Tokyo, residues were detected in 3 out of 26 deep-fried chickens, 5 out of 20 non-fried chicken cutlets, and 17 out of 39 chicken muscles.


Assuntos
Resíduos de Drogas/análise , Análise de Alimentos/métodos , Extração Líquido-Líquido/métodos , Carne/análise , Drogas Veterinárias/análise , Animais , Galinhas , Cromatografia Líquida de Alta Pressão , Músculos/química , Espectrometria de Massas em Tandem
19.
Shokuhin Eiseigaku Zasshi ; 58(1): 26-31, 2017.
Artigo em Japonês | MEDLINE | ID: mdl-28260729

RESUMO

Two yellow dyes, together with tartrazine (Y4), were found in cucumbers pickled in soy sauce, for which the use of tartrazine is permitted, by TLC, LC-DAD, and LC-MS. The retention times on LC chromatograms and the maximum absorbance wavelengths measured by LC-DAD of the two dyes were different from those of tartrazine. Mass spectra of the dyes indicated that these dyes lacked one sulfonyl group of tartrazine. The presence of two less sulfonated dyes in tartrazine has been reported. Hence, the two less sulfonated dyes were synthesized. The two dyes found in cucumbers were compared with the synthesized dyes by LC-DAD and LC-MS. Since the retention times of the dyes in cucumbers on the LC chromatograms, as well as their LC-DAD spectra and mass spectra, were found to be identical with those of the synthesized dyes, we concluded these dyes are the less sulfonated subsidiary dyes of tartrazine.


Assuntos
Cucumis sativus/química , Análise de Alimentos/métodos , Corantes de Alimentos/análise , Corantes de Alimentos/química , Contaminação de Alimentos/análise , Conservação de Alimentos , Alimentos de Soja/análise , Tartrazina/análise , Tartrazina/química , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Cromatografia em Camada Delgada , Espectroscopia de Ressonância Magnética , Espectrometria de Massas
20.
J Chromatogr B Analyt Technol Biomed Life Sci ; 1044-1045: 142-148, 2017 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-28107701

RESUMO

A simultaneous determination of amantadine, rimantadine, and memantine in processed products (deep-fried chicken, fried chicken, fried quail egg, and grilled chicken) with liquid chromatography tandem mass spectrometry (LC-MS/MS) was developed. This new method was also applicable for chicken tissue (muscle, liver, and gizzard) and eggs. The chromatographic separation was performed on a Kinetex® XB-C18 core-shell technology column using a mobile phase of acetonitrile and 0.1% formic acid in a 10mmol/L ammonium formate solution, resulting in the complete separation of isomers (rimantadine and memantine) and any other obstructive peaks from the sample matrices. Sample preparation was performed by a modified QuEChERS method using acetonitrile and a 0.1% acetic acid extraction solution and cleaned using an Oasis® MCX cartridge. The sample matrix had no effect on the identification of the compounds. For quantification, an external solvent calibration curve was used. This new method exhibited good accuracy ranging from 79.9% to 91.5%. The relative standard deviation of repeatability (RSDr) ranged from 1.2% to 3.6% and the relative standard deviation of within-laboratory reproducibility (RSDWR) ranged from 1.3% to 6.0%. These standard deviations satisfied the criteria for Japanese validation guidelines. The limit of quantification (LOQ) was 1.0µg/kg for all samples. Analyte residues were not detected in 55 samples using the validated method.


Assuntos
Adamantano/análise , Cromatografia Líquida/métodos , Ovos/análise , Carne/análise , Espectrometria de Massas em Tandem/métodos , Adamantano/química , Adamantano/isolamento & purificação , Animais , Galinhas , Modelos Lineares , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
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