Development of prostate cancer diagnostic marker targeting glycosylation

• Project/Area Number: 26430145
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor diagnostics
• Research Institution: Tohoku Medical and Pharmaceutical University (2015-2016); Juntendo University (2014)
• Principal Investigator: FUJIMURA Tsutomu 東北医科薬科大学, 薬学部, 教授 (70245778)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 前立腺がん / 診断マーカー / 糖タンパク質 / 糖鎖修飾ペプチド / IgGの糖鎖 / anti IgG 抗体 / anti Hpt 抗体 / Luminex / 診断マーカーカー / 糖鎖修飾ペプチド抗体 / anti Hpt抗体 / anti IgG抗体 / ELISA / Luminexビーズ / 診断マーカ-

Outline of Final Research Achievements

Prostate specific antigen (PSA) is used for diagnosis of prostate cancer, but detection range called gray zone, 4-10 ng / ml, includes benign disease patients 70%. An unnecessary biopsy is performed in patients with benign diseases at present. The cancer-specific glycosylated peptide antibodies were prepared from haptoglobin (Hpt) and IgG from prostate cancer patient serum. I have developed a multiplex bead bound antibody detection method capable of simultaneous measurement of multiple items. The glycosylation amounts of Hpt and IgG in Serum between prostate cancer patients, benign diseases patients, and healthy subjects were compared. As a result, changes in prostate cancer-specific sugar chain structure could be confirmed in cancer patients. The possibility to distinguish between cancer patient and benign disease patient or healthy individual can doing. These results demonstrated the possibility of definitive diagnosis that does not require biopsy of prostate cancer.

Research Products

• [Journal Article] Glycosylation status of serum immunoglobulin G in patients with prostate diseases. (2016)
  • Author(s): Kazuno S, Furukawa JI, Shinohara Y, Murayama K, Fujime M, Ueno T, Fujimura T.
  • Journal Title: Cancer Medicine Volume: - Issue: 6 Pages: 1137-1146
  • DOI: 10.1002/cam4.662
  • Peer Reviewed / Open Access
• [Journal Article] Integrative genomic and proteomic analyses identifies glycerol-3-phosphate acyltransferase as a target of low-dose ionizing radiation in EBV infected-B cells (2016)
  • Author(s): Tabe, Y., Hatanaka, Y., Nakashiro, M., Sekihara, K., Yamamoto, S., Matsushita, H., Kazuno, S., Fujimura, T., Ikegami, T., Nakanaga, K., Matsumoto, H., Ueno, T., Aoki, J., Yokomizo, T., Konopleva, M., Andreeff, M., Miida, T., Iwabuchi, K.,Sasai, K.
  • Journal Title: Int J Radiat Biol Volume: 92 Issue: 1 Pages: 24-34
  • DOI: 10.3109/09553002.2015.1106021
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Protein Expression Profiling of Giant Cell Tumors of Bone Treated with Denosumab. (2016)
  • Author(s): Mukaihara K, Suehara Y, Kohsaka S, Akaike K, Tanabe Y, Kubota D, Ishii M, Fujimura T, Kazuno S, Okubo T, Takagi T, Yao T, Kaneko K, Saito T.
  • Journal Title: PLoS One Volume: 10 Issue: 2 Pages: e0148401-e0148401
  • DOI: 10.1371/journal.pone.0148401
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Expression of F-actin-capping protein subunit beta is associated with cell growth and motility in epithelioid sarcoma. (2016)
  • Author(s): Mukaihara K, Suehara Y*, Kohsaka S, Kubota D, Toda-Ishii M, Akaike K, Fujimura T, Kobayashi E, Yao T, Ladanyi, M, Kaneko K, Saito T.
  • Journal Title: BMC cancer. Volume: 16(1) Issue: 1 Pages: 206-206
  • DOI: 10.1186/s12885-016-2235-z
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Bioinformatic identification of cytochrome b5 homologues from the parasitic nematode Ascaris suum and the free-living nematode Caenorhabditis elegans highlights the crucial role of A. suum adult-specific secretory cytochrome b5 in parasitic adaptation. (2015)
  • Author(s): Takamiya S, Hashimoto M, Mita T, Yokota T, Nakajima Y, Yamakura F, Sugio S,
  • Journal Title: Parasitol Int. Volume: 65 Issue: 2 Pages: 113-20
  • DOI: 10.1016/j.parint.2015.11.004
  • Peer Reviewed
• [Journal Article] Cysteine protease antigens cleave CD123, the α subunit of murine IL-3 receptor, on basophils and suppress IL-3-mediated basophil expansion (2015)
  • Author(s): Nishikado H, Fujimura T, Taka H, Mineki R, Ogawa H, Okumura K, Takai T
  • Journal Title: Biochem Biophys Res Commun Volume: 印刷中 Issue: 2 Pages: 261-266
  • DOI: 10.1016/j.bbrc.2015.03.022
  • Peer Reviewed / Open Access
• [Journal Article] A clinically attainable dose of L-asparaginase targets (2015)
  • Author(s): Sugimoto K, Suzuki HI, Fujimura T, Ono A, Kaga N, Isobe Y, Sasaki M, Taka H,
  • Journal Title: Cancer Sci. Volume: 106 Issue: 11 Pages: 1534-1543
  • DOI: 10.1111/cas.12807
  • Peer Reviewed / Open Access
• [Journal Article] Ribosomal biogenesis and translational flux inhibition by the selective inhibitor of nuclear export (SINE) XPO1 antagonist KPT-185. (2015)
  • Author(s): Yoko Tabe, Kensuke Kojima, Shinichi Yamamoto, Kazumasa Sekihara, Hiromichi Matsushita, Richard Eric Davis, Zhiqiang Wang, Wencai Ma, Jo Ishizawa, Saiko Kazuno, Michael Kauffman, Sharon Shacham, Tsutomu Fujimura, Takashi Ueno, Takashi Miida, Michael Andreef
  • Journal Title: PLoS One Volume: 10 Issue: 9 Pages: e0137210-e0137210
  • DOI: 10.1371/journal.pone.0137210
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Secreted tyrosine sulfated-eIF5A mediates oxidative stress-induced apoptosis. (2015)
  • Author(s): Seko Y, Fujimura T, Yao T, Taka H, Mineki R, Okumura K, Murayama K.
  • Journal Title: Sci Rep. Volume: 8;5 Issue: 1 Pages: 13737-13751
  • DOI: 10.1038/srep13737
  • Peer Reviewed / Open Access
• [Journal Article] The novel combination of dual mTOR inhibitor AZD2014 and pan-PIM inhibitor AZD1208 inhibits growth in acute myeloid leukemia via HSF pathway suppression. (2015)
  • Author(s): Harada M, Benito J, Yamamoto S, Kaur S, Arslan D, Ramirez S, Jacamo R, Platanias L, Matsushita H, Fujimura T, Kazuno S, Kojima K, Tabe Y, Konopleva M.
  • Journal Title: Oncotarget Volume: 6 Issue: 35 Pages: 37930-37947
  • DOI: 10.18632/oncotarget.6122
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Absence of Elovl6 attenuates steatohepatitis but promotes gallstone formation in a (2015)
  • Author(s): Kuba M, Matsuzaka T, Matsumori R, Saito R, Kaga N, Taka H, Ikehata K, Okada N,
  • Journal Title: Sci Rep. Volume: 5 Issue: 1 Pages: 17604-17604
  • DOI: 10.1038/srep17604
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Structural insight into amino group-carrier protein-mediated lysine biosynthesis: crystal structure of the LysZ•LysW complex from Thermus thermophilus (2015)
  • Author(s): Ayako Yoshida, Takeo Tomita, Tsutomu Fujimura, Chiharu Nishiyama, Tomohisa Kuzuyama, and Makoto Nishiyama
  • Journal Title: Journal of Biological Chemistry Volume: 290 Issue: 1 Pages: 435-447
  • DOI: 10.1074/jbc.m114.595983
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A treadmill exercise reactivates the signaling of the mammalian target of rapamycin (mTor) in the skeletal muscles of starved mice. (2015)
  • Author(s): Zheng DM, Bian Z, Furuya N, Oliva Trejo JA, Takeda-Ezaki M, Takahashi K, Hiraoka Y, Mineki R, Taka H, Ikeda S, Komatsu M, Fujimura T, Ueno T, Ezaki J.
  • Journal Title: Biochem Biophys Res Commun Volume: 456 Pages: 519-526
  • Peer Reviewed
• [Journal Article] Effects of sitagliptin on ectopic fat contents and glucose metabolism in type 2 diabetic patients with fatty liver: A pilot study (2014)
  • Author(s): Watanabe T, Tamura Y, Kakehi S, Funayama T, Takeno K, Kawaguchi M, Yamamoto L, Sato F, Ikeda S, Taka H, Fujimura T, Fujitani Y, Kawamori R, Watada H
  • Journal Title: J Diabetes Invest Volume: Mar;6(2) Issue: 2 Pages: 164-72
  • DOI: 10.1111/jdi.12262
  • Peer Reviewed / Open Access
• [Journal Article] The human cathelicidin LL-37 host defense peptide upregulates tight junction-related proteins and increases human epidermal keratinocyte barrier function. (2014)
  • Author(s): Akiyama T, Niyonsaba F, Kiatsurayanon C, Nguyen TT, Ushio H, Fujimura T, Ueno T, Okumura K, Ogawa H, Ikeda S
  • Journal Title: J Innate Immun Volume: 6 Issue: 6 Pages: 739-53
  • DOI: 10.1159/000362789
  • Peer Reviewed / Open Access
• [Journal Article] Increased expression of ERp57/GRP58 is protective against pancreatic beta cell death caused by autophagic failure. (2014)
  • Author(s): Yamamoto E, Uchida T, Abe H, Taka H, Fujimura T, Komiya K, Hara A, Ogihara T, Fujitani Y, Ueno T, Takeda S, Watada H.
  • Journal Title: Biochem Biophys Res Commun Volume: 453 Issue: 1 Pages: 19-24
  • DOI: 10.1016/j.bbrc.2014.09.040
  • Peer Reviewed / Open Access
• [Presentation] 新規末梢性掻痒治療薬の代謝物への影響 (2016)
  • Author(s): 藤村 務
  • Organizer: 第10回メタボロームシンポジウム
  • Place of Presentation: 慶応義塾大学（山形県鶴岡市）
  • Year and Date: 2016-10-19
• [Presentation] セサミンのK562細胞に対する抗腫瘍効果の解析 (2016)
  • Author(s): 藤村 務, 渡部 彩佳, 猪股 明日香, 久保田 雅史, 蓬田 伸
  • Organizer: 第89回日本生化学会大会
  • Place of Presentation: 仙台国際センター（宮城県仙台市）
  • Year and Date: 2016-09-25
• [Presentation] Carbohydrate chain structure analysis of Acute Phase Proteins included in prostate cancer (2016)
  • Author(s): 藤村 務
  • Organizer: 平成28年度 化学系学協会東北大会
  • Place of Presentation: いわき明星大学（福島県いわき市）
  • Year and Date: 2016-09-10
  • Invited
• [Presentation] LC-ESI-MS/MSによるコルチゾール生合成関連ステロイドの一斉分析 (2016)
  • Author(s): 小松 祥子、 榊 教克、 今 華恵, 藤村 務、山下 幸和
  • Organizer: 日本薬学会第１３６年会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市みなとみらい）
  • Year and Date: 2016-03-26
• [Presentation] レクチンを活用した前立腺がん特異的糖鎖構造変化およびキャリア糖タンパク質の同定 (2016)
  • Author(s): 數野 彩子, 藤村 務, 上野 隆
  • Organizer: 第89回日本生化学会大会
  • Place of Presentation: 仙台国際センター（宮城県仙台市）
• [Presentation] GC/MSによる呼気分析の進歩 (2016)
  • Author(s): 藤村 務
  • Organizer: 第17回アロマ・サイエンス・フォーラム 2016
  • Place of Presentation: アルカディア市ヶ谷（東京都千代田区）
  • Invited
• [Presentation] GC/MSによる呼気分析 (2015)
  • Author(s): 藤村 務
  • Organizer: 第341回ガスクロマトグラフィー研究懇談会
  • Place of Presentation: 北トピア13F飛鳥ホール（東京都北区王子）
  • Year and Date: 2015-12-11
  • Invited
• [Presentation] 造血器腫瘍細胞におけるGlnの関与 (2015)
  • Author(s): 藤村 務、杉本耕一、加賀直子、高 ひかり
  • Organizer: 第五回新アミノ酸分析研究会
  • Place of Presentation: 東京大学武田先端知ビル（東京都文京区本郷）
  • Year and Date: 2015-12-07
• [Presentation] 妊娠中の摂取カロリー制限母ラットからの出生仔でみられたグルココルチコイドフィード (2015)
  • Author(s): 根本 崇宏、 藤村 務、加賀 直子、 高 ひかり、 上野 隆、 柿沼 由彦
  • Organizer: BMB2015
  • Place of Presentation: 神戸ポートアイランド（兵庫県神戸市中央区港島中町）
  • Year and Date: 2015-12-01
• [Presentation] オートファジーの抑制は代謝および転写リプログラミングを引き起こす (2015)
  • Author(s): 斉藤 哲也、和栗 聡、 藤村 務、 上野 隆、田口 恵子、本橋 ほづみ、 山本 雅之、 曽我 朋義、 田中 啓二、 小松 雅明
  • Organizer: BMB2015
  • Place of Presentation: 神戸ポートアイランド（兵庫県神戸市中央区港島中町）
  • Year and Date: 2015-12-01
• [Presentation] ヒスタミンH4受容体を標的とした新規末梢性掻痒治療薬の機能解析 (2015)
  • Author(s): 藤村 務, 櫻田 忍
  • Organizer: BMB2015
  • Place of Presentation: 神戸ポートアイランド（兵庫県神戸市中央区港島中町）
  • Year and Date: 2015-12-01
• [Presentation] LC-ESI-MS/MSによる血清グルココルチコイドおよび前駆体の一斉分析 (2015)
  • Author(s): 小松 祥子, 齋藤 彩夏, 榊 教克, 今 華恵, 齋藤 滋, 藤村 務, 山下 幸和
  • Organizer: 第54回日本薬学会東北支部大会
  • Place of Presentation: 岩手医科大学矢巾キャンパス（岩手県紫波郡矢巾町西徳田）
  • Year and Date: 2015-09-26
• [Presentation] ．硫化水素の高感度生物発光検出法の開発 (2015)
  • Author(s): 岩渕 理子, 大野 賢一, 山下 幸和, 藤村 務
  • Organizer: 第54回日本薬学会東北支部大会
  • Place of Presentation: 岩手医科大学矢巾キャンパス（岩手県紫波郡矢巾町西徳田）
  • Year and Date: 2015-09-26
• [Presentation] 改良Marfey法を用いた微生物細胞内アミノ酸の検出法に関する検討 (2015)
  • Author(s): 加藤 創, 高橋 和弘, 原田 健一, 山下 幸和, 藤村 務
  • Organizer: 第54回日本薬学会東北支部大会
  • Place of Presentation: 岩手医科大学矢巾キャンパス（岩手県紫波郡矢巾町西徳田）
  • Year and Date: 2015-09-26
• [Presentation] 新規末梢性掻痒治療薬の機能解析 (2014)
  • Author(s): ○藤村 務、數野 彩子、櫻田 忍
  • Organizer: 第87回日本生化学会大会
  • Place of Presentation: 京都国際会議場
  • Year and Date: 2014-10-15 – 2014-10-18
• [Presentation] 蛍光ビーズ－レクチンマルチプレックス糖鎖検出法による前立腺がん診断 (2014)
  • Author(s): ○數野 彩子、上野 隆、藤村 務
  • Organizer: 第87回日本生化学会大会
  • Place of Presentation: 京都国際会議場
  • Year and Date: 2014-10-15 – 2014-10-18
• [Presentation] Search of cancer markers in exhaled breath. (2014)
  • Author(s): ○Fujimura T, Matsumori S, Kaga K, Taka H, Kajiyama Y, Ueno T.
  • Organizer: Metabolomics 2014
  • Place of Presentation: Ymagata-ken Tsuruoka-shi
  • Year and Date: 2014-06-23 – 2014-06-26
• [Book] 寄生虫学研究：材料と方法 2014年度版 (2015)
  • Author(s): 藤村 務、村山季美枝
  • Total Pages: 179
  • Publisher: 三恵社
• [Remarks] 臨床分析化学
  • URL: http://www.tohoku-mpu.ac.jp/pharmacy/about/lp_a04/
• [Remarks] 順天堂大学大学院研究基盤センター生体分子研究室
  • URL: http://www.juntendo.ac.jp/graduate/laboratory/labo/seitai_bunshi/