Papers - KAKIZAKI Ikuko
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Machine learning diagnosis by immunoglobulin <i>N</i> ‐glycan signatures for precision diagnosis of urological diseases
Hiromichi Iwamura, Kei Mizuno, Shusuke Akamatsu, Shingo Hatakeyama, Yuki Tobisawa, Shintaro Narita, Takuma Narita, Shinichi Yamashita, Sadafumi Kawamura, Toshihiko Sakurai, Naoki Fujita, Hirotake Kodama, Daisuke Noro, Ikuko Kakizaki, Shigeyuki Nakaji, Ken Itoh, Norihiko Tsuchiya, Akihiro Ito, Tomonori Habuchi, Chikara Ohyama, Tohru Yoneyama
Cancer Science 113 ( 7 ) 2434 - 2445 2022.5
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A simple quality evaluation method for proteoglycan after addition to beverages
Ikuko Kakizaki and Yoji Kato
J. Appl. Glycosci. 69 ( 2 ) 45 - 48 2022.3
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Effect of glycosaminoglycan structure on all-trans-retinoic acid-induced neural differentiation of P19 embryonal carcinoma cells
Ikuko Kakizaki, Takayasu Kobayashi, Shinri Tamura, Hiroshi Akagi, Keiichi Takagaki
Biochemical and Biophysical Research Communications 570 169 - 174 2021.9
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N-glycan signature of serum immunoglobulins as a diagnostic biomarker of urothelial carcinomas.
Hirotake Kodama, Tohru Yoneyama, Toshikazu Tanaka, Daisuke Noro, Yuki Tobisawa, Hayato Yamamoto, Shinichiro Suto, Shingo Hatakeyama, Kazuyuki Mori, Takahiro Yoneyama, Yasuhiro Hashimoto, Ikuko Kakizaki, Shigeyuki Nakaji, Chikara Ohyama
Cancer medicine 2021.1
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Essential hyaluronan structure for binding with hyaluronan-binding protein (HABP) determined by glycotechnological approach.
Shinichiro Suto, Ikuko Kakizaki, Yota Tatara, Masahiko Endo
Carbohydrate polymers 251 116989 - 116989 2021.1
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A chondroitin sulfate chain of urinary trypsin inhibitor enhances protease inhibitory activity of the core protein
Yu Teshigahara, Ikuko Kakizaki, Wataru Hirao, Kanji Tanaka, and Ryoki Takahashi
Journal of Applied Glycoscience 2020
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Hyaluronan synthesis inhibitor 4-methylumbelliferone affects extracellular matrix components in cultured human skin fibroblasts
Yasufumi Endo, Genn Takahashi, Ikuko Kakizaki, and Masahiko Endo
Hirosaki Med. J. 70 ( 1 ) 1 - 12 2019.11
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Dermatan sulfate oligosaccharides having reducing end 2, 5-anhydro-d-talose inhibit bovine testicular hyaluronidase activity.
Carbohydrate research 483 107754 - 107754 2019.9
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Proteoglycan-substrate gel zymography for the detection of chondroitin sulfate-degrading enzymes.
Takashi Kobayashi, Ikuko Kakizaki, Toshiya Nakamura
Analytical biochemistry 568 51 - 52 2019.3
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Development of new therapeutic agents of preterm birth by glycosaminoglycan
2019.3
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4-Methylumbelliferone Decreases the Hyaluronan-rich Extracellular Matrix and Increases the Effectiveness of 5-Fluorouracil.
Eri Yoshida, Daisuke Kudo, Hayato Nagase, Akiko Suto, Hiroshi Shimoda, Shinichiro Suto, Ikuko Kakizaki, Masahiko Endo, Kenichi Hakamada
Anticancer research 38 ( 10 ) 5799 - 5804 2018.10
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Characterization of Proteoglycan and Hyaluronan in Hot Water Extract from Salmon Cartilage
Kakizaki, I., Miura, A., Mineta, T., Hong, J., and Kato, Y.
Journal of Applied Glycoscience 64 ( 4 ) 83 - 90 2017.11
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A mechanism for evasion of CTL immunity by altered O-glycosylation of HLA class I.
Mihoko Sutoh Yoneyama, Yuki Tobisawa, Shingo Hatakeyama, Misaki Sato, Kiyoshi Tone, Yota Tatara, Ikuko Kakizaki, Tomihisa Funyu, Minoru Fukuda, Senji Hoshi, Chikara Ohyama, Shigeru Tsuboi
Journal of biochemistry 161 ( 6 ) 479 - 492 2017.6
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Chondroitin sulfate proteoglycans from salmon nasal cartilage inhibit angiogenesis.
Takashi Kobayashi, Ikuko Kakizaki, Hiroyuki Nozaka, Toshiya Nakamura
Biochemistry and biophysics reports 9 72 - 78 2017.3
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4-Methylumbelliferone Suppresses Hyaluronan Synthesis and Tumor Progression in SCID Mice Intra-abdominally Inoculated With Pancreatic Cancer Cells.
Hayato Nagase, Daisuke Kudo, Akiko Suto, Eri Yoshida, Shinichiro Suto, Mika Negishi, Ikuko Kakizaki, Kenichi Hakamada
Pancreas 46 ( 2 ) 190 - 197 2017.2
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Hyaluronan Production Regulates Metabolic and Cancer Stem-like Properties of Breast Cancer Cells via Hexosamine Biosynthetic Pathway-coupled HIF-1 Signaling.
Theerawut Chanmee, Pawared Ontong, Tomomi Izumikawa, Miho Higashide, Nobutoshi Mochizuki, Chatchadawalai Chokchaitaweesuk, Manatsanan Khansai, Kazuki Nakajima, Ikuko Kakizaki, Prachya Kongtawelert, Naoyuki Taniguchi, Naoki Itano
The Journal of biological chemistry 291 ( 46 ) 24105 - 24120 2016.11
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Antitumor effects of the hyaluronan inhibitor 4-methylumbelliferone on pancreatic cancer.
Eri Yoshida, Daisuke Kudo, Hayato Nagase, Hiroshi Shimoda, Shinichiro Suto, Mika Negishi, Ikuko Kakizaki, Masahiko Endo, Kenichi Hakamada
Oncology letters 12 ( 4 ) 2337 - 2344 2016.10
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Effects of C-xylopyranoside derivative on epithelial regeneration in an in vitro 3D oral mucosa model.
Atsushi Uenoyama, Ikuko Kakizaki, Aki Shiomi, Naoaki Saito, Yuko Hara, Taro Saito, Hisashi Ohnuki, Hiroko Kato, Ritsuo Takagi, Takeyasu Maeda, Kenji Izumi
Bioscience, biotechnology, and biochemistry 80 ( 7 ) 1344 - 1355 2016.7
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サケ軟骨熱水抽出物 (ヒアルコPG) の経口摂取による日焼け抑制効果―無作為化二重盲検プラセボ対照並行群間比較試験―
後藤 昌史, 末川 裕, 花田 友香子, 柿崎 育子, 山本 和司, 加藤 陽治
日本応用糖質科学会誌 応用糖質科学 6 ( 2 ) 138 - 146 2016.5
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Benefical effect of 4-methylumbelliferone against bile duct ligation-induced hepatic fibrosis rats
Naoya Sawada, Kenichiro Mikami, Go Igarashi, Tetsu Endo, Ken Sato, Ikuko Kakizaki, and Shinsaku Fukuda
The Hirosaki Medical Journal 66 ( 2-4 ) 143 - 151 2016.3
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Enzymatic synthesis of hyaluronan hybrid urinary trypsin inhibitor.
Ikuko Kakizaki, Ryoki Takahashi, Miho Yanagisawa, Futaba Yoshida, Keiichi Takagaki
Carbohydrate research 413 129 - 134 2015.9
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Characterization of Proteoglycan and Hyaluronan in Water-based Delipidated Powder of Salmon Cartilage
Kakizaki I., Miura, A., Ito, S., Mineta, T., Hong, J.S., and Kato, Y.
Journal of Applied Glycoscience 62 ( 3 ) 115 - 120 2015.9
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Inhibitory effect of chondroitin sulfate oligosaccharides on bovine testicular hyaluronidase.
Ikuko Kakizaki, Hideyo Koizumi, Fengchao Chen, Masahiko Endo
Carbohydrate polymers 121 362 - 371 2015.5
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Chondroitin sulfate cluster of epiphycan from salmon nasal cartilage defines binding specificity to collagens.
Yota Tatara, Ikuko Kakizaki, Shinichiro Suto, Haruna Ishioka, Mika Negishi, Masahiko Endo
Glycobiology 25 ( 5 ) 557 - 569 2015.5
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Biochemical and atomic force microscopic characterization of salmon nasal cartilage proteoglycan.
Ikuko Kakizaki, Takashi Mineta, Mana Sasaki, Yota Tatara, Eiji Makino, Yoji Kato
Carbohydrate polymers 103 538 - 549 2014.3
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One set system for the synthesis and purification of glycosaminoglycan oligosaccharides reconstructed using a hyaluronidase-immobilized column.
Shinichiro Suto, Ikuko Kakizaki, Toshiya Nakamura, Masahiko Endo
Biopolymers 2014.3
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Effect of a cholesterol-rich lipid environment on the enzymatic activity of reconstituted hyaluronan synthase.
Pawared Ontong, Yasuyo Hatada, Shun'ichiro Taniguchi, Ikuko Kakizaki, Naoki Itano
Biochemical and biophysical research communications 443 ( 2 ) 666 - 671 2014.1
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Synthesis of N-acetyl glucosamine analogs as inhibitors for hyaluronan biosynthesis.
Gilbert Wasongaa, Yota Tatarab, Ikuko Kakizaki, Xuefei Huanga
Journal of Carbohydrate Chemistry 32 392 - 409 2013.9
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Epiphycan from salmon nasal cartilage is a novel type of large leucine-rich proteoglycan.
Yota Tatara, Ikuko Kakizaki, Yoshiyuki Kuroda, Shinichiro Suto, Haruna Ishioka, Masahiko Endo
Glycobiology 23 ( 8 ) 993 - 1003 2013.8
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Time-dependent gene expression and immunohistochemical analysis of the injured anterior cruciate ligament.
T Naraoka, Y Ishibashi, E Tsuda, Y Yamamoto, T Kusumi, I Kakizaki, S Toh
Bone & joint research 1 ( 10 ) 238 - 244 2012.10
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Hyaluronan-chondroitin hybrid oligosaccharides as new life science research tools.
Ikuko Kakizaki, Shinichiro Suto, Yota Tatara, Toshiya Nakamura, Masahiko Endo
Biochemical and biophysical research communications 423 ( 2 ) 344 - 349 2012.6
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Interaction of Listeria monocytogenes autolysin amidase with glycosaminoglycans promotes listerial adhesion to mouse hepatocytes.
Krisana Asano, Ikuko Kakizaki, Akio Nakane
Biochimie 94 ( 6 ) 1291 - 1299 2012.6
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Anti-inflammatory effect of proteoglycan and progesterone on human uterine cervical fibroblasts.
Asami Fukuyama, Kanji Tanaka, Ikuko Kakizaki, Kosuke Kasai, Mitsuru Chiba, Toshiya Nakamura, Hideki Mizunuma
Life sciences 90 ( 13-14 ) 484 - 488 2012.4
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Effects of divalent cations on bovine testicular hyaluronidase catalyzed transglycosylation of chondroitin sulfates.
Kakizaki, I., Nukatsuka, I., Takagaki, K., Majima, M., Iwafune, M., Suto, S., Endo, M.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 406 ( 2 ) 239 - 244 2011.3
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Analysis of functional sugar chains of proteoglycan in the urine from woman with osteoporosis.
Abe, K., Higuchi, T., Mizunuma, H., Kakizaki, I., Endo, M., and Suto, S.
Hirosaki Med. J. 61 ( 2-4 ) 97 - 103 2011.3
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Identification of proteoglycan from salmon nasal cartilage.
Kakizaki, I., Tatara, Y., Majima, M., Kato, Y., Endo, M.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS 506 ( 1 ) 58 - 65 2011.2
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Method for hybrid synthesis of glycosaminoglycan chains Utilizing Chemo-enzymatic Procedures.
Yamaguchi, M., Kakizaki, I., and Endo, M.
J. Carbohyd. Chem. 29 315 - 331 2010.11
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Mechanism for the hydrolysis of hyaluronan oligosaccharides by bovine testicular hyaluronidase.
Kakizaki, I., Ibori, N., Kojima, K., Yamaguchi, M., Endo M.
FEBS Journal 277 ( 7 ) 1776 - 1786 2010.4
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Novel proteoglycan glycotechnology: chemoenzymatic synthesis of chondroitin sulfate-containing molecules and its application.
Masanori Yamaguchi, Keiichi Takagaki, Kaoru Kojima, Naohiro Hayashi, Fengchao Chen, Ikuko Kakizaki, Atsushi Kon, Masahiko Endo
Glycoconjugate journal 27 ( 1 ) 189 - 198 2010.1
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Novel products in hyaluronan digested by bovine testicular hyaluronidase.
Chen, F., Kakizaki, I., Yamaguchi, M., Kojima, K., Takagaki, K., and Endo, M.
Glycoconj. J. 26 ( 5 ) 559 - 566 2009.11
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Stimulation of small proteoglycan synthesis by the hyaluronan synthesis inhibitor 4-methylumbelliferone in human skin fibroblasts.
Funahashi, M., Nakamura, T., Kakizaki, I., Mizunuma, H., and Endo, M.
Connect Tissue Res. 50 ( 3 ) 194 - 202 2009.7
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Structural Interactions in Chondroitin 4-Sulfate-mediated Adherence of Plasmodium falciparum-infected Erythrocytes in Human Placenta During Pregnancy-Associated Malaria.
Achur RN, Kakizaki I, Goel S, Kojima K, Madhunapantula SV, Goyal A, Ohta M, Kumar S, Takagaki K, Gowda DC.
Biochemistry 47 ( 47 ) 12635 - 12643 2008.11
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Up-regulation of hyaluronan synthase genes in cultured human epidermal keratinocytes by UVB irradiation.
Kakizaki, I., Itano, N., Kimata, K., Hanada, K., Kon, A., Yamaguchi, M., Takahashi, T., Takagaki, K.
Archives of biochemistry and biophysics 471 ( 1 ) 85 - 93 2008.3
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Inhibitory effect of 4-methylesculetin on hyaluronan synthesis slows the development of human pancreatic cancer in vitro and in nude mice.
Morohashi, H., Yoshihara, S., Nakai, M., Yamaguchi, M., Kakizaki, I., Kon, A., Sasaki, M., and Takagaki, K.
International journal of cancer 120 ( 12 ) 2704 - 2709 2007.6
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Diversity in the degree of sulfation and chain length of the glycosaminoglycan moiety of urinary trypsin inhibitor isomers.
Kakizaki, I., Takahashi, R., Ibori, N., Kojima, K., Takahashi, T., Yamaguchi, M., Kon, A., and Takagaki, K.
Biochimica et biophysica acta 1770 ( 2 ) 171 - 177 2007.2
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Efficient and widely applicable method of constructing neo-proteoglycan utilizing copper(I) catalyzed 1,3-dipolar cycloaddition.
Yamaguchi, M., Kojima, K., Hayashi, N., Kakizaki, I., Kon A., and Takagaki, K.
Tetrahedron Letter 47 ( 42 ) 7455 - 7458 2006.8
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Study of hyaluronan synthase inhibitor, 4-methylumbelliferone derivatives on human pancreatic cancer cell (KP1-NL).
Morohashi, H., Kon, A., Nakai, M., Yamaguchi, M., Kakizaki, I., Yoshihara S., Sasaki, M., and Takagaki, K.
Biochemical and biophysical research communications 345 ( 4 ) 1454 - 1419 2006.7
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The effects of glycosaminoglycans on thrombopoietin-induced megakaryocytopoiesis.
Kashiwakura, I., Teramachi, T., Kakizaki, I., Takagi, Y., Takahashi, T. A., and Takagaki, K.
Haematologica 91 ( 4 ) 445 - 451 2006.4
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The glycophorin C N-linked glycan is a critical component of the ligand for the Plasmodium falciparum erythrocyte receptor BAEBL.
Mayer, D.C., Jiang, L., Achur, R.N., Kakizaki, I., Gowda, D.C., and Miller, L.H.
Proceedings of the National Academy of Sciences of the United States of America 103 ( 7 ) 2358 - 2362 2006.2
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4-methylumbelliferone, a hyaluronan synthase suppressor, enhances the anticancer activity of gemcitabine in human pancreatic cancer cells.
Nakazawa, H., Yoshihara, S., Kudo, D., Morohashi, H., Kakizaki, I., Kon, A., Takagaki, K., and Sasaki, M.
Cancer chemotherapy and pharmacology Links 57 ( 2 ) 165 - 170 2006.1
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A hyaluronan synthase suppressor, 4-methylumbelliferone, inhibits liver metastasis of melanoma cells.
Yoshihara S., Kon A., Kudo D., Nakazawa H., Kakizaki I., Sasaki M., Endo M., and Takagaki K.
FEBS letters 579 ( 12 ) 2722 - 2726 2005.5
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Effect of a hyaluronan synthase suppressor, 4-methylumbelliferone, on B16F-10 melanoma cell adhesion and locomotion.
Kudo, D., Kon, A., Yoshihara, S., Kakizaki, I., Sasaki, M., Endo, M., and Takagaki, K.
Biochemical and biophysical research communications 321 ( 4 ) 783 - 787 2004.9
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A novel mechanism for the inhibition of hyaluronan biosynthesis by 4-methylumbeliifieron.
Kakizaki, I., Kojima, K., Takagaki, K., Endo, M., Kannagi, R., Ito, M., Maruo, Y., Sato, H., Yasuda, T., Mita, S., Kimata, K., and Itano, N.
The Journal of biological chemistry 279 ( 32 ) 33281 - 33289 2004.8
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Structural characterization of the bovine tracheal chondroitin sulfate chains and binding of Plasmodium falciparum-infected erythrocytes.
Muthusamy, A., Achur, R. N., Valiyaveettil, M., Madhunapantula, S. V., Kakizaki, I., Bhavanandan, V. P., and Gowda, C. D.
Glycobiology 14 ( 7 ) 635 - 645 2004.7
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Inhibition of 3T3-L1 adipocyte differentiation by 6-ethoxyzolamide: repressed peroxisome proliferator-activated receptor gamma mRNA and enhanced CCAAT/enhancer binding protein beta mRNA levels.
Takahata, T., Kumano, T., Ookawa, K., Hayakari, M., Kakizaki, I., and Tsuchida, S.
Biochemical pharmacology 67 ( 9 ) 1667 - 1675 2004.5
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A glycomic approach to proteoglycan with a two-dimensional polysaccharide chain map.
Iwafune, M., Kakizaki, I., Nakazawa, H., Nukatsuka, I., Endo, M., and Takagaki, K.
Analytical biochemistry 325 ( 1 ) 35 - 40 2004.2
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A novel Sp1-family-related cis-acting element for transcription of type VII collagen gene (COL7A1).
Hideyuki Sasaki, Atsushi Kon, Hitoshi Takeda, Daisuke Sawamura, Ikuko Kakizaki, Keiichi Takagaki, Isao Hashimoto, Katsumi Hanada
Journal of dermatological science 32 ( 3 ) 239 - 242 2003.9
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Reconstruction of glycosaminoglycan chains in decorin.
Mito Iwafune, Ikuko Kakizaki, Masahiro Yukawa, Daisuke Kudo, Sakae Ota, Masahiko Endo, Keiichi Takagaki
Biochemical and biophysical research communications 297 ( 5 ) 1167 - 1170 2002.10
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Inhibition of hyaluronan synthesis in Streptococcus equi FM100 by 4-methylumbelliferone.
Ikuko Kakizaki, Keiichi Takagaki, Yasufumi Endo, Daisuke Kudo, Hitoshi Ikeya, Teruzo Miyoshi, Bruce A Baggenstoss, Valarie L Tlapak-Simmons, Kshama Kumari, Akio Nakane, Paul H Weigel, Masahiko Endo
European journal of biochemistry / FEBS 269 ( 20 ) 5066 - 5075 2002.10
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Activation of mouse Pi-class glutathione S-transferase gene by Nrf2(NF-E2-related factor 2) and androgen.
Hiromi Ikeda, Mohamed S Serria, Ikuko Kakizaki, Ichiro Hatayama, Kimihiko Satoh, Shigeki Tsuchida, Masami Muramatsu, Shinzo Nishi, Masaharu Sakai
The Biochemical journal 364 ( Pt 2 ) 563 - 570 2002.6
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Cleavage of the xylosyl serine linkage between a core peptide and a glycosaminoglycan chain by cellulases.
Keiichi Takagaki, Mito Iwafune, Ikuko Kakizaki, Keinosuke Ishido, Yoji Kato, Masahiko Endo
The Journal of biological chemistry 277 ( 21 ) 18397 - 18403 2002.5
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Carriers for enzymatic attachment of glycosaminoglycan chains to peptide.
Keiichi Takagaki, Keinosuke Ishido, Ikuko Kakizaki, Mito Iwafune, Masahiko Endo
Biochemical and biophysical research communications 293 ( 1 ) 220 - 224 2002.4
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Domain structure of chondroitin sulfate E octasaccharides binding to type V collagen.
Keiichi Takagaki, Hidekazu Munakata, Ikuko Kakizaki, Mito Iwafune, Taito Itabashi, Masahiko Endo
The Journal of biological chemistry 277 ( 11 ) 8882 - 8889 2002.3
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Studies on sugar chain elongation in cultured human colon adenocarcinoma cells using 4-methylumbelliferyl glycoside derivatives and p-nitrophenyl glycoside derivatives as artificial primers.
Kukidome, J., Kakizaki, I., Takagaki, K., and Endo, M.
Hirosaki Med. J. 194 ( 1 ) 59 - 65 2001.10
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The mechanism of cell death in human cultured colon adenocarcinoma cell line COLO 201 induced by beta-D-N-acetylglucosaminyl-p-nitrophenol.
J Kukidome, I Kakizaki, K Takagaki, A Matsuki, A Munakata, M Endo
The Tohoku journal of experimental medicine 194 ( 1 ) 23 - 34 2001.5
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Induction of apoptosis and cell cycle arrest in mouse colon 26 cells by benastatin A.
I Kakizaki, K Ookawa, T Ishikawa, M Hayakari, T Aoyagi, S Tsuchida
Japanese journal of cancer research : Gann 91 ( 11 ) 1161 - 1168 2000.11
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Enzymatic reconstruction of dermatan sulfate.
K Takagaki, H Munakata, I Kakizaki, M Majima, M Endo
Biochemical and biophysical research communications 270 ( 2 ) 588 - 593 2000.4
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Chimeric glycosaminoglycan oligosaccharides synthesized by enzymatic reconstruction and their use in substrate specificity determination of Streptococcus hyaluronidase.
K Takagaki, H Munakata, M Majima, I Kakizaki, M Endo
Journal of biochemistry 127 ( 4 ) 695 - 702 2000.4
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Identification of glutathione S-transferase p-1 as the class pi form dominantly expressed in mouse hepatic adenomas.
K Ookawa, H Nakano, I Kakizaki, I Hatayama, H Kajihara-Kano, J Kimura, M Hayakari, T Takahata, K Satoh, S Tsuchida
Japanese journal of cancer research : Gann 89 ( 6 ) 641 - 648 1998.6
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Epitope mapping of a monoclonal antibody to human glutathione transferase P1-1 the binding of which is inhibited by glutathione.
T Takahata, S Tsuchida, M Oomura, T Matsumoto, J Azumi, I Hatayama, M Hayakari, J Kimura, I Kakizaki, H Kano, K Satoh, K Sato
The Biochemical journal 321 ( Pt 2) 531 - 536 1997.1
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Lentinan enhances sensitivity of mouse colon 26 tumor to cis-diamminedichloroplatinum (II) and decreases glutathione transferase expression.
T Murata, I Hatayama, I Kakizaki, K Satoh, K Sato, S Tsuchida
Japanese journal of cancer research : Gann 87 ( 11 ) 1171 - 1178 1996.11
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cDNA and deduced amino acid sequence of human PK-120, a plasma kallikrein-sensitive glycoprotein.
H Nishimura, I Kakizaki, T Muta, N Sasaki, P X Pu, T Yamashita, S Nagasawa
FEBS letters 357 ( 2 ) 207 - 211 1995.1
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Identification and cDNA cloning of single-stranded DNA binding proteins that interact with the region upstream of the human c-myc gene.
Y Negishi, Y Nishita, Y Saëgusa, I Kakizaki, I Galli, F Kihara, K Tamai, N Miyajima, S M Iguchi-Ariga, H Ariga
Oncogene 9 ( 4 ) 1133 - 1143 1994.4
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Cell cycle-dependent activation of C-myc enhancer.
I Kakizaki, Y Imamura, I Galli, F Kihara, H Ariga, S Iguchiariga
International journal of oncology 2 ( 4 ) 657 - 661 1993.4