| 1. |
- Fukuda, Tetsuya, et al.
(author)
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A selected reaction monitoring mass spectrometric assessment of biomarker candidates diagnosing large-cell neuroendocrine lung carcinoma by the scaling method using endogenous references
- 2017
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:4
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Journal article (peer-reviewed)abstract
- Selected reaction monitoring mass spectrometry (SRM-MS) -based semi-quantitation was performed to assess the validity of 46 selected candidate proteins for specifically diagnosing large-cell neuroendocrine lung carcinoma (LCNEC) and differentiating it from other lung cancer subtypes. The scaling method was applied in this study using specific SRM peak areas (AUCs) derived from the endogenous reference protein that normalizes all SRM AUCs obtained for the candidate proteins. In a screening verification study, we found that seven out of the 46 candidate proteins were statistically significant for the LCNEC phenotype, including 4F2hc cell surface antigen heavy chain (4F2hc/CD98) (p-ANOVA ≤ 0.0012), retinal dehydrogenase 1 (p-ANOVA ≤ 0.0029), apolipoprotein A-I (p-ANOVA ≤ 0.0004), β-enolase (p-ANOVA ≤ 0.0043), creatine kinase B-type (p-ANOVA ≤ 0.0070), and galectin- 3-binding protein (p-ANOVA = 0.0080), and phosphatidylethanolamine-binding protein 1 (p-ANOVA ≤ 0.0012). In addition, we also identified candidate proteins specific to the smallcell lung carcinoma (SCLC) subtype. These candidates include brain acid soluble protein 1 (p-ANOVA < 0.0001) and γ-enolase (p-ANOVA ≤ 0.0013). This new relative quantitationbased approach utilizing the scaling method can be applied to assess hundreds of protein candidates obtained from discovery proteomic studies as a first step of the verification phase in biomarker development processes.
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| 2. |
- Fukuda, Tetsuya, et al.
(author)
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An Improvement on MS-based Epigenetic Analysis of Large Histone-derived Peptides by Using the IVU Interface.
- 2015
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In: Analytical Biochemistry. - : Elsevier BV. - 1096-0309 .- 0003-2697. ; 486:Online 05 June 2015, s. 14-16
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Journal article (peer-reviewed)abstract
- Highly protonated histone-derived peptides impede a sufficient mass spectrometry (MS) -based epigenetic analysis since their relatively low m/z due to a high degree of proton addition to peptides would difficult to analyze the resulting complex MS/MS spectra. In order to reduce the degree of protonations, we have developed a new interface, the IVU, in which peptides are ionized under a vaporized organic solvent, and it has demonstrated that the doubly-charged histone-tail H2B peptide, PEPAKSAPAPKKGSKKAVTKAQKK (m/z 1238.243 , +2), has been detected by using the IVU interface and sequenced, which was not detectable before.
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| 3. |
- Kato, Harubumi, et al.
(author)
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A Clinician View and Experience of Proteomic Studies in the Light of Lung Cancer in Japanese Healthcare
- 2011
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In: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 10:1, s. 51-57
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Journal article (other academic/artistic)abstract
- In Japan, rising costs have impacted the framework of maintaining an efficient and effective healthcare system. Today, urgent implementation of programs to address this need have led to a rebuilding of the entire approach of medical evaluation and clinical care. Recent developments in clinical proteomics based on mass spectrometry (MS) for identifying, sequencing, and quantifying disease-relevant protein biomarkers is a promising means for optimal drug prescription using biomarker diagnosis. We illustrate in this report our experience with lung cancer cases with various drug therapies evaluated with proteomics studies.
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| 4. |
- Nakayama, Noboru, et al.
(author)
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Developments of mass spectrometry-based technologies for effective drug development linked with clinical proteomes.
- 2016
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In: Drug Metabolism and Pharmacokinetics. - : Elsevier BV. - 1347-4367. ; 31:1, s. 3-11
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Research review (peer-reviewed)abstract
- A strong demand in drug discovery and development today is to overcome "Big Gaps" encountered by differences in species and races, to accelerate effective developments in cost and time, and to meet medical needs. Moreover, drugs of various types have emerged which cover middle-size molecules and polymers rather than conventional small molecules. Upon those challenges, mass spectrometry (MS)-based technologies, which will be described in this paper, will play an increasingly important role, among which the liquid chromatography-tandem mass spectrometry (LC/MS/MS) platform will be powerful as rapid and molecule-based analysis more than ever. nanoPore Optical Interferometry (nPOI) newly introduced can detect even weak interactions in protein-protein and protein-compound, and can be connected directly to LC/MS/MS for identification of binding molecular species, which will be quite useful for affinity ranking and high-throughput interaction screening. Imaging MS provides the molecular information and spatial distribution of targeted molecules within a tissue specimen. MS-based clinical proteomics utilizing clinical specimens and empowered by advanced bioinformatics can attain both key protein-protein interaction (PPI) networks with major protein players responsible for functional mechanisms of a disease subtype. An integration of those MS-based technologies will deliver a seamless platform of drug development from molecules identified in human clinical specimens.
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| 5. |
- Nishimura, Toshide, et al.
(author)
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Clinical initiatives linking Japanese and Swedish healthcare resources on cancer studies utilizing Biobank Repositories.
- 2014
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In: Clinical and Translational Medicine. - : Wiley. - 2001-1326. ; 3:1
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Journal article (peer-reviewed)abstract
- The Tokyo Medical University Hospital in Japan and the Lund University hospital in Sweden have recently initiated a research program with the objective to impact on patient treatment by clinical disease stage characterization (phenotyping), utilizing proteomics sequencing platforms. By sharing clinical experiences, patient treatment principles, and biobank strategies, our respective clinical teams in Japan and Sweden will aid in the development of predictive and drug related protein biomarkers. Data from joint lung cancer studies are presented where protein expression from Neuro- Endocrine lung cancer (LCNEC) phenotype patients can be separated from Small cell- (SCLC) and Large Cell lung cancer (LCC) patients by deep sequencing and spectral counting analysis. LCNEC, a subtype of large cell carcinoma (LCC), is characterized by neuroendocrine differentiation that small cell lung carcinoma (SCLC) shares. Pre-therapeutic histological distinction between LCNEC and SCLC has so far been problematic, leading to adverse clinical outcome. An establishment of protein targets characteristic of LCNEC is quite helpful for decision of optimal therapeutic strategy by diagnosing individual patients. Proteoform annotation and clinical biobanking is part of the HUPO initiative (http://www.hupo.org) within chromosome 10 and chromosome 19 consortia.
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