Nittobo Medical Co.

Tokyo, Japan

Nittobo Medical Co.

Tokyo, Japan
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Satoh M.,Chiba University | Takano S.,Chiba University | Sogawa K.,Chiba University | Sogawa K.,Azabu University | And 9 more authors.
Cancer Science | Year: 2017

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies. To improve its outcome, reliable biomarkers are urgently needed. In this study, we aimed to elucidate the key molecules involved in PDAC progression using proteomics approaches. First, we undertook 2-D electrophoresis to identify the proteins overexpressed in PDAC tissues. Following the analysis of agarose gel spots, cofilin-1 was identified and verified as a candidate protein commonly upregulated in PDAC tissues. In immunohistochemistry, cofilin-1 was strongly expressed in the cytoplasm of PDAC cells. Samples were divided into two groups based on the level of cofilin-1 expression. The high expression group showed significantly higher incidence of hematogenous dissemination in relapsed patients than the low expression group (P = 0.0083). In in vitro experiments, knockdown of cofilin-1 significantly decreased chemotaxis in PDAC cell lines. After we confirmed that cofilin-1 was secreted from PDAC cells, we established a detection system for the immune-complex of cofilin-1 in sera. Using this system, we measured the IC levels of cofilin-1 in sera and observed that the IC levels of cofilin-1 in PDAC patients were higher than those in healthy volunteers and patients with pancreatitis (PDAC vs. healthy volunteers, P < 0.0001; PDAC vs. patients with pancreatitis, P < 0.026). Notably, the IC levels of cofilin-1 showed a stepwise increase during PDAC progression (P = 0.0034), and high IC levels of cofilin-1 indicated poor prognosis of patients after surgery (P = 0.039). These results suggest that the IC of cofilin-1 in sera is a potentially attractive serum biomarker for the prognosis of PDAC. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Sato N.,Nittobo Medical Co. | Sato N.,Osaka Prefecture University | Wakabayashi M.,Nittobo Medical Co. | Nakatsuji M.,Osaka Prefecture University | And 9 more authors.
Biochemical and Biophysical Research Communications | Year: 2017

Hyper-activation of the MAPK and PI3K-AKT pathways is linked to tumour progression in triple-negative breast cancer (TNBC). However, clinically effective predictive markers for drugs targeted against protein kinases involved in these pathways have not been identified. We investigated the ability of MEK and PI3K catalytic activity to predict sensitivity to trametinib and wortmannin in TNBC. MEK and PI3K activities correlated strongly with each other only in cell lines showing wortmannin-specific sensitivity, as shown by a linear regression curve (R = 0.951). Accordingly, we created a new parameter that distinguishes trametinib and wortmannin sensitivity in vitro and in vivo. Our findings suggest that the catalytic activities of MEK and PI3K might predict the response of TNBC to trametinib and wortmannin. © 2017 The Authors

Ihara H.,Toho University | Watanabe T.,University of Hyogo | Hashizume N.,Wayo Women's University | Totani M.,Showa Women's University | And 17 more authors.
Annals of Clinical Biochemistry | Year: 2010

Background: The aim of the present study was to evaluate standard reference material (SRM) 1955 commutability as a reference material for serum folate using automated methods. We also designed so as to reduce the intermethod variability present in different automated methods. Methods: Using a microbiological assay related to the 'information value' of SRM 1955 as a comparison method, we investigated the possibility of standardization for the assay values of serum folate as measured by the automated methods (Access, Centaur and Elecsys). In the assay of 50 patient sera by these automated methods, we corrected observed values by the SRM 1955 and compared with comparison values. Results: The observed values of SRM 1955 Levels I, II and III were within or outside (but near) a 95% prediction interval obtained from patient sera by the automated methods. The normalized residuals obtained from SRM 1955 were within ± 3.0 (in SD units), which enabled us to conclude that the SRM 1955 had a physicochemical characterization similar to native serum. Twelve patients were assessed as hypofolataemia (<6.0 ng/mL) and 38 patients as normal (≥6.0 ng/mL). Before correction, folate levels in six of 12 patients were lower than 6.0 ng/mL, and those in seven of 38 patients were higher than 6.0 ng/mL with the automated methods. After correction, low levels were found in four of 12 patients, and normal levels were found in 33 of 38 patients. Conclusions: The use of SRM 1955 would help to reduce the intermethod variability present in different automated methods for serum folate measurement.

Kubo H.,Tohoku University | Suzuki T.,Tohoku University | Matsushima T.,Sysmex Corporation | Ishihara H.,Sysmex Corporation | And 6 more authors.
BMC Cancer | Year: 2014

Background: Lung cancer is one of the leading causes of cancer death worldwide. Even with complete resection, the prognosis of early-stage non-small cell lung cancer is poor due to local and distant recurrence, and it remains unclear which biomarkers are clinically useful for predicting recurrence or for determining the efficacy of chemotherapy. Recently, several lines of evidence have indicated that the enzymatic activity of cyclin-dependent kinases could be a clinically relevant prognostic marker for some cancers. We investigated whether the specific activity of cyclin-dependent kinases 1 and 2 could predict recurrence or death in early non-small cell lung cancer patients.Methods: Patients with newly diagnosed, pathologically confirmed non-small cell lung cancer were entered into this blinded cohort study. The activity of cyclin-dependent kinases was determined in 171 samples by the C2P® assay, and the results were subjected to statistical analysis with recurrence or death as a clinical outcome.Results: The Cox proportional hazards model revealed that the activity of cyclin-dependent kinase 1, but not 2, was a predictor of recurrence, independent of sex, age, and stage. By contrast, cyclin-dependent kinase 2 activity was a predictor of death, independent of sex and stage.Conclusion: This study suggested the possible clinical use of cyclin-dependent kinase 1 as a predictor of recurrence and cyclin-dependent kinase 2 as a predictor of overall survival in early-stage non-small cell lung cancer. Thus, a combination of activity of cyclin-dependent kinases 1 and 2 is useful in decision-making regarding treatment strategies for non-small cell lung cancer after surgery. © 2014 Kubo et al.; licensee BioMed Central Ltd.

The detection of a non-alcoholic steatohepatitis patient and the accurate discrimination between a normal person and a non-alcoholic steatohepatitis patient can be achieved by measuring alanine-glyoxylate amino transferase in a sample.

The detection of a non-alcoholic steatohepatitis patient and the accurate discrimination between a normal person and a non-alcoholic steatohepatitis patient can be achieved by measuring alanine-glyoxylate amino transferase in a sample.

Noda K.,Nittobo Medical Co | Sato Y.,Nittobo Medical Co | Miura T.,Nittobo Medical Co | Katayama K.,Nittobo Medical Co | Kojima R.,Nittobo Medical Co
Annals of Clinical Biochemistry | Year: 2010

Background: Chlorophosphonazo-III (2,7-bis[4-chloro-2-phosphonophenylazo]- 1,8-dihydroxy-3,6-naphthalenedisulphonic acid, disodium salt; CPZ-III) reacts with calcium and magnesium in a sample under acidic to neutral conditions. However, the specific method of measuring calcium in serum using CPZ-III has not been established because of the difficulty of avoiding the interaction between CPZ-III and albumin. Methods: In this study, we found that the non-specific reaction between CPZ-III and albumin could be controlled and calcium in serum could be specifically detected using CPZ-III combined with vanadate. On the basis of this finding, we evaluated a novel method of serum calcium determination using CPZ-III. Results: This CPZ-III vanadate method gave linear results from 0 to 7.0 mmol/L. The coefficient of variation was 0.63-0.76%. There was no interference except with Omniscan. There was no change in control performance during 60 d under open-air conditions. The assay results correlated well with those of the Arsenazo-III (2,7-bis(2-arsonophenylazo)-1,8-dihydroxy-3, 6-naphthalenedisulphonic acid) method (slope = 1.067; intercept = 20.120; r = 0.989; Sy/x = 0.036 mmol/L), o-cresolphthalein complexone method (slope = 0.911; intercept = 0.186; r = 0.988; Sy/x = 0.035 mmol/L), amylase enzymatic method (slope = 0.981; intercept = 0.072; r = 0.989; Sy/x = 0.036 mmol/L) and inductively coupled plasma emission spectroscopy method (slope = 0.955; intercept = 20.001; r = 0.979; Sy/x = 0.048 mmol/L). Conclusions: These results suggested that the present method has great clinical potential for measuring calcium.

Takeuchi M.,Nittobo Medical Co. | Takeuchi M.,Osaka Prefecture University | Kondo K.,Osaka Prefecture University | Kuri H.,Osaka Prefecture University | And 3 more authors.
Journal of the Electrochemical Society | Year: 2012

Cu via-filling is an essential technology for fabricating signal lines both on chips and on printed circuit boards and also through a silicon via in 3D wafer lever packaging for electrical devices. Generally, four additives, such as suppressors, accelerators, levelers and chloride ions, are added to a Cu electrodeposition bath in order to achieve bottom-up filling. The selection of additives and control of the additive concentrations are complex and cause increased cost and complicated quality control. In order to solve these problems, we succeeded in developing a bottom-up filling technique using only one additive, which has four types of functions. This additive is a diallylmethylamine copolymer, and contains cationic nitrogen, chloride ion and sulfur dioxide in its structure. The counter ion of the diallylmethylamine copolymer was the chloride ion or bromide ion. They were synthesized from the monomer with anions in an aqueous solution by radical polymerization. The surface morphology and cross sections of the electrodeposits were observed by scanning electron microscopy (SEM) and optical microscopy (OM). Linear sweep voltammetry (LSV) and quartz crystal microbalance (QCM) analyses were conducted. © 2012 The Electrochemical Society.

Kikuchi W.,Chiba University | Kikuchi W.,Nittobo Medical Co. | Nishimura M.,Chiba University | Kuga T.,Kyoto Pharmaceutical University | And 7 more authors.
Clinical Proteomics | Year: 2016

Background: Fibrinogen alpha C chain 5.9 kDa fragment (FIC5.9) is a new serum biomarker for chronic hepatitis that was discovered by proteomics analysis. Previous studies have shown that FIC5.9 is derived from the C-terminal region of fibrinogen alpha chain and the serum levels of FIC5.9 decrease in chronic hepatitis. It also have been reported that FIC5.9 cannot be detected in the blood stream of the systemic circulation and it is released from fibrinogen during blood clotting in collecting tube. However, the mechanism of FIC5.9 releasing from fibrinogen is unclear. Methods: We formulated a hypothesis that FIC5.9 is released by enzymes that are activated by post-blood collection and may be coagulation and fibrinolysis factors. In this study, we analyzed the mechanisms of FIC5.9 releasing from fibrinogen in healthy blood. Results: Our analysis showed that thrombin acts as an initiator for FIC5.9 releasing, and that mainly plasmin cleaves N-terminal end of FIC5.9 and neutrophil elastase cleave C-terminal end of FIC5.9. Conclusion: FIC5.9 reflects minute changes in coagulation and fibrinolysis factors and may be associated with pathological conditions. © 2016 The Author(s).

Noda K.,Nittobo Medical Co. | Noda K.,Chiba University | Sogawa K.,Chiba University | Kikuchi W.,Nittobo Medical Co. | And 10 more authors.
Proteomics - Clinical Applications | Year: 2011

Purpose: We previously identified novel biomarker candidates in heavy consumers of alcohol using serum proteome analysis. Among several candidates, a 5.9kDa peptide identified as a fragment of the fibrinogen alpha C chain (FIC5.9) was the most promising. To move FIC5.9 toward potential diagnostic use, we developed an enzyme immunoassay that enables measurement of serum FIC5.9 levels. Experimental design: Two monoclonal antibodies specific to the N and C-termini of the 5.9-kDa peptide were used to develop a FIC5.9 sandwich ELISA. The assay was evaluated by comparing the results with those obtained by the stable isotope-labeled dilution mass spectrometry (SID-MS) using the ClinProt™ system. Results: The ELISA results correlated with the SID-MS findings (slope=0.795, intercept=-0.011, r2=0.908) and the performance of the ELISA was satisfactory in terms of recovery (98.5-103.0%) and within-run (1.4-4.7%) and between-day (2.8-8.4%) reproducibility. The assay was capable of detecting changes in FIC5.9 during abstinence from drinking in patients with alcohol dependency (p<0.0001). Conclusions and clinical relevance: The sandwich ELISA developed in this study will be useful for validation of the diagnostic significance of serum FIC5.9 levels in various pathological conditions, including alcoholism. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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