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Verification of Wisteria floribunda agglutinin-positive glycoproteins as a cholangiocarcinoma marker
Atsushi Matsuda,Atsushi Kuno,Hideki Matsuzaki,Toru Kawamoto,Toshihide Shikanai,Yasuni Nakanuma,Masakazu Yamamoto,Nobuhiro Ohkohchi,Yuzuru Ikehara,Junichi Shoda,Jun Hirabayashi,Hisashi Narimatsu 한국당과학회 2012 한국당과학회 학술대회 Vol.2012 No.1
Cholangiocarcinoma (CC) is a lethal malignancy which exhibits asymptomatic growth infiltrating the surrounding structures, and thus,CC is usually detected at an advanced stage. The mainstay of treatment for CC is complete resection with negative surgical margins. Therefore, its diagnosis at a relatively early stage is demanded for performing the surgical resection. Since the definitive CC diagnosis relies on invasive methods such as biliary cytology and biopsy, a noninvasive assay with high diagnostic accuracy is keenly required. In the previous meeting, we reported that Wisteria floribunda agglutinin (WFA) is the best probe lectin which reliably distinguishes between CC and normal bile duct epithelia in tissue sections. Moreover, L1 cell adhesion molecule (L1CAM), CA125, and maspin were assigned as the reliable CC marker candidates by WFA-assisted glycoproteomics and immunohistochemistry. In this meeting, we will introducethe verification and validation process in one of the above candidates, L1CAM. Since the serum concentration of L1CAM was low as described in other reports (< 5 ng/mL), we firstly constructed a highly-sensitive detection system to confirm the existence of L1CAM in both bile and serum of CC patients with immunoprecipitation and western blotting. We then performed highly-sensitive glycan profiling with antibody-assisted lectin microarray (limit of detection: 25 pg) and confirmed WFA-positivity of biliary L1CAM from the CC patients. The subsequent validation study using bile samples from CC patients (n = 29) and patients with benign bile duct diseases (n = 29) showed that WFA-positive L1CAM distinguished CC from the benigndiseases with good specificity (sensitivity = 0.66, specificity = 0.93, overall accuracy = 0.79, area under the receiver operating curve [AUC] = 0.82). The combined use of the L1CAM assay with the highly-sensitive assay detecting WFA-positive sialylated mucin 1 (WFA-sialyl MUC1), a reliable CC marker (Matsuda A., et al., Hepatology, 2010), sufficiently improved the diagnostic accuracy of CC (overall accuracy = 0.84, AUC = 0.93). This combination assay using WFA–L1CAM and WFA–sialyl MUC1 will possibly be a useful serological test with enhanced reliability.
Atsushi Kuno,Masaharu Nomura,Hideki Matsuzaki,Tomoko Nakagawa,Atsushi Matsuda,Yoshitoshi Hirao,Masao Sasaki,Norihiro Ikeda,Toshitaka Nagao,Yuzuru Ikehara,Hisashi Narimatsu 한국당과학회 2012 한국당과학회 학술대회 Vol.2012 No.1
Cell glycome is defined by the glyco synthesis machinery regulated by harmonized expression of more than 100 glycogenes. The machinery-dependent glycome drastically shifts during cell progression and differentiation in association with tumorigenesis and malformation, and thus it motivates us to discover the disease-related alteration in glycosylation. Glycan-targeted histochemical approaches using lectin and anti-glycogene antibodies have provided some key information to characterize specific histological types of cells in pathology. However, this approach is not suitable for the comprehensive analysis targeting the cell glycome, and thus may fail to provide insight into glycome shift during the disease progression. Several years ago, we developed the methodology for rapid and systematic glycome shift analysis targeting formalin-fixed tissue specimens by means of lectin microarray. The resultant method enabled simultaneous observation of over 40 lectins interacted with glycoproteins in 1 mm2 of the tissue specimens. Recently, we sophisticated this methodology to be suitable for comparative analysis of a series of cells in specific groups isolated from a single tissue specimen by laser microdissection, and now our research has gained interest in the variability and distribution of cell glycome in the tissue, i.e., “tissue glycome mapping”. In this meeting, we will summarize the advantage of this new methodology and its application for glyco-biomarker discovery, as well as the construction of “tissue glycome atlas”.
Kaori Shoji,Kaori Shoji,Masanobu Tsubaki,Yuzuru Yamazoe,Takao Satou,Tatsuki Itoh,Yasuhiro Kidera,Yoshihiro Tanimori,Masashi Yanae,Hideaki Matsuda,Atsushi Taga,Haruyuki Nakamura,Shozo Nishida 대한약학회 2011 Archives of Pharmacal Research Vol.34 No.3
Mangiferin, 1,3,6,7-tetrahydroxyxanthone-C2-β-D-glucoside (C-glucosylxanthone), is a xanthone derivative that is widely distributed in higher plants. Recently, mangiferin was found to exhibit potential antitumor effects. However, the molecular mechanisms of this effect have not been elucidated. In the present study, we attempt to clarify the mechanism of mangiferininduced apoptosis in the human acute myeloid leukemia cell line HL-60; mangiferin was found to induce apoptosis. We also observed a concurrent increase in caspase-3 activity and DNA fragmentation. Furthermore, on examining the survival signals expressed during apoptotic induction, we observed that mangiferin caused a remarkable decrease in the nuclear entry of NF-κB p65. However, there were no changes in the expression of other survival signals,such as extracellular signal-regulated kinase 1/2, protein kinase B, and p38 mitogenactivated protein kinase. In addition, mangiferin suppressed the expressions of Bcl-xL and XIAP; however, we did not note any changes in the levels of Bcl-2, Bax, and Bim. These results indicate that mangiferin induces apoptosis by suppressing NF-κB activation and expressions of Bcl-xL and XAIP. These findings suggest that mangiferin may be useful as an anticancer agent and can be used in combination therapy with other anticancer drugs for the treatment of acute myeloid leukemia.
Kim, Yun Kyoung,Oh, Ji Hee,Kim, Young Jin,Hwang, Mi Yeong,Moon, Sanghoon,Low, Siew-Kee,Takahashi, Atsushi,Matsuda, Koichi,Kubo, Michiaki,Lee, Juyoung,Kim, Bong-Jo Hindawi Publishing Corporation 2015 BioMed research international Vol.2015 No.-
<P>Hematological traits are important health indicators and are used as diagnostic clinical parameters for human disorders. Recently, genome-wide association studies (GWAS) identified many genetic loci associated with hematological traits in diverse ethnic groups. However, additional GWAS are necessary to elucidate the breadth of genetic variation and the underlying genetic architecture represented by hematological metrics. To identify additional genetic loci influencing hematological traits (such as hematocrit, hemoglobin concentration, white blood cell count, red blood cell count, and platelet count), we conducted GWAS and meta-analyses on data from 12,509 Korean individuals grouped into population-based cohorts. Of interest is EGF, a factor plays a role in the proliferation and differentiation of hematopoietic progenitor cells. We identified a novel EGF variant, which associated with platelet count in our study (<I>P</I><SUB>combined</SUB> = 2.44 × 10<SUP>−15</SUP>). Our study also replicated 16 genetic associations related to five hematological traits with genome-wide significance (<I>P</I> < 5 × 10<SUP>−8</SUP>) that were previously established in other ethnic groups. Of these, variants influencing platelet count are distributed across several genes and have pleiotropic effects in coronary artery disease and dyslipidemia. Our findings may aid in elucidating molecular mechanisms underlying not only hematopoiesis but also inflammatory and cardiovascular diseases.</P>