Vol.5 No.3 2012

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Research paper : Development of basic tools for glycoscience and their application to cancer diagnosis (H. Narimatsu)−214−Synthesiology - English edition Vol.5 No.3 (2012) the establishment of cancer diagnosis systems are remarkably described.It is noteworthy that the author regarded the development of basic technology tools, which are accessible for use by many scientists and engineers, as the first target aiming for the future enhancement of a new scientific field, glycoscience. Scientists are apt to gather under a fully developed fruitful tree and wish to become an end-user of fashionable sciences, but often avoid seeding or growing young trees of basic science. In contrast, this approach by the author and his team is worth praise as leading a new scientific field for other researchers.Moreover, I think that the establishment of the three main themes, “synthesis”, “structure”, and “functions and biomarkers” at the initial phase as shown in Figure 2 was the key to the steady growth of the following research activities. I am sure that, to successfully lead the big project under a solid scenario, intensive and concerted efforts by a large group such as a research center of AIST for a long period as 10 years were necessary, as the author describes in “6. Conclusion.” Comment (Noboru Yumoto, AIST)The development of the elemental technologies for analysis of glycan structures by a multi-disciplinary approach and the integration of the elemental technologies in accordance with the scenario of developing the disease biomarker is a great example of “Type 2 Basic Research.” 2 Domestic and international application of the basic toolsQuestion (Akira Ono)I assume that the basic tools developed in this research are broadly utilized in Japan and overseas to enhance glycoscience. Please introduce some of the examples for current application of these developmental achievements by other research groups of other institutes and companies. Are there any collaborative researches with domestic or international organizations? If so, please let us know as much as possible.Answer (Hisashi Narimatsu)Here is a list for some of the applications that I know of for our-developed basic tools used by other organizationsGlycogenes • We hold the patent for about 30 glycogenes, and granted the licenses of 13 genes to GlycoGeneInc.• We provide unpatented glycogenes for about 20 domestic and oversea research organizations. Moreover, we deposited these glycogenes to the National Institute of Technology and Evaluation (NITE) for wider distribution.• Our developed glycogene database, GGDB had 172,570 access/year (2011fy).• We developed 13 strains of glycogene knock-out mice. Collaborative studies with 5 domestic institutes and 3 overseas institutes are ongoing using them as disease models.• Collaborative studies of glycan synthesis by glycosyltransferases aiming at applications such as to glycan arrays are ongoing with domestic and overseas institutes.• A collaborative study for glycoprotein synthesis using inexpensively expressed glycosyltransferases by yeast is ongoing with a private company.• Many research articles have been published as achievements of collaborative studies.Lectin microarray • GP Biosciences Ltd. commercialized the lectin microarray• More than a few tens of related reports are published from external organizations. I picked three important reports that have a strong impact. The first report is the utilization of lectin microarray for evaluation of iPS cells by Dr. Yamanaka of Kyoto University:YC. Wang et al.: Specific lectin biomarkers for isolation of human pluripotent stem cells identified through array-based glycomic analysis, Cell Res., 21(11), 155-1563 (2011).EL. Bird-Lieberman et al.: Molecular imaging using fluorescent lectins permits rapid endoscopic identification of dysplasia in Berrett’s esophagus, Nature Medicine, 18(2), 315-321 (2012).SA. Fry et al.: Lectin microarray profiling of metastatic breast cancers, Glycobiology, 21(8), 1060-1070 (2011).• The Lectin Frontier Database, LfDB, had 23,605 accesses in 2011.• We have already applied for seven patents concerning glycan biomarkers based on the lectin array. Glycan structure analysis based on the mass spectrometry• The system has been marketed from Shimadzu Corporation/Mitsui Knowledge Industry Co., Ltd. They sold one system each to Qatar, Beijing, Shanghai, and the United States, and three in Japan (one each for National Cancer Center, Gifu University, and Japan Anti-Doping Agency).• The access counts to the two databases were 18,256 for GMDB and 36,729 for GPDB in 2011.• We have many accomplishments of collaborative studies in glycan structure analyses. These are some of the representative articles. T. Fukuda et al.: 1,6-fucosyltransferase-deficient mice exhibit multiple behavioral abnormalities associated with a schizophrenia-like phenotype: importance of the balance between the dopamine and serotonin systems, J. Biol. Chem., 286(21), 18434-18443 (2011).N. Watanabe et al.: Clinicopathological features of 171 cases of primary thyroid lymphoma: a long-term study involving 24 553 patients with Hashimoto’s disease, Br. J. Haematol., 153(2), 236-243 (2011).T. Nakagawa et al.: Glycomic analyses of glycoproteins in bile and serum during rat hepatocarcinogenesis, J. Proteome Res., 9(10), 4888-4896 (2010).N. Sasaki et al.: High levels of E4-PHA-reactive oligosaccharides: potential as marker for cells with characteristics of hepatic progenitor cells, Glycoconj. J., 26(9), 1213-1223 (2009).H. Suzuki et al.: Computationally and experimentally derived general rules for fragmentation of various glycosyl bonds in sodium adduct oligosaccharides, Anal. Chem., 81(3), 1108-1120 (2009).H. Shirato et al.: Noroviruses distinguish between type 1 and type 2 histo-blood group antigens for binding, J. Virol., 82(21), 10756-10767 (2008). YY. Fan et al.: Identification of further elongation and branching of dimeric type 1 chain on lactosylceramides

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