Investigation of tumor heterogeneity through analyses of local distribution of tissue metabolites using imaging mass spectrometry

• Project/Area Number: 22501034
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Tumor diagnosis
• Research Institution: Keio University
• Principal Investigator: WAKUI Masatoshi 慶應義塾大学, 医学部, 講師 (90240465)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2012: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2010: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: がんの個性診断 / 腫瘍組織 / 顕微質量分析 / 代謝物 / 不均一性 / がん / 代謝適応 / in vivoモデル / 臨床検体

Research Abstract

We successfully detected local distribution of tissue metabolites by imaging mass spectrometry to reveal the tumor heterogeneity formed by metabolic adaptation. These results provide insights into the metabolomic aspects of tumor biology, aiding in the de

Research Products

• [Journal Article] Overexpression of the miR-34 family suppresses invasive growth of malignant melanoma with the wild-type p53 gene. (2012)
  • Author(s): Yamazaki H, Chijiwa T, Inoue Y, Abe Y, Suemizu H, Kawai K, Wakui M, Furukawa D, Mukai M, Kuwao S, Saegusa M, Nakamura M.
  • Journal Title: Exp Ther Med. Volume: 3 (5) Pages: 793-796
  • Peer Reviewed
• [Journal Article] Overexpression of the miR-34 family suppresses invasive growth of malignant melanoma with the wild-type p53 gene. (2012)
  • Author(s): Yamazaki H
  • Journal Title: Experimental and Therapeutic Medicine Volume: 3 Pages: 793-796
  • Peer Reviewed
• [Journal Article] Development of imaging mass spectrometry (IMS) dataset extract software, IMS convolution. (2011)
  • Author(s): Hayasaka T, Goto-InoueN, Ushijima M, Yao I, Yuba-Kubo A, Wakui M, Shigeki Kajihara S, Matsuura M, Setou M
  • Journal Title: Anal. Bioanal. Chem. Volume: 401 (1) Pages: 183-193
  • Peer Reviewed
• [Journal Article] Semi-quantitative analyses of metabolic systems of human colon cancer metastatic xenografts in livers of superimmunodeficient NOG mice (2011)
  • Author(s): KuboA, Ohmura M,Wakui M, Takeshita K, Harad T, Kajihara S, Ogawa K, SuemizuH, Nakamura M, Setou M, Suematsu M.
  • Journal Title: Anal. Bioanal. Chem. Volume: 400 (7) Pages: 1895-1904
  • Peer Reviewed
• [Journal Article] Lovastatin and valproic acid additively attenuate cell invasion in ACC-MESO-1 cells. (2011)
  • Author(s): Yamauchi Y, Izumi Y, Asakura K, Fukutomi T, Serizawa A, Kawai K, Wakui M, Suematsu M, Nomori H.
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 410 (2) Pages: 328-332
  • Peer Reviewed
• [Journal Article] The cytostatic effects of lovastatin on ACC-MESO-1 cells. (2011)
  • Author(s): Asakura K, Izumi Y, Yamamoto M, Yamauchi Y, Kawai K, Serizawa A, Mizushima, T, Ohmura M, Kawamura M, Wakui M, Adachi T, Nakamura M, Suematsu M, Nomori H.
  • Journal Title: J. Surg. Res. Volume: 170 (2)
  • Peer Reviewed
• [Journal Article] The reconstituted 'humanized liver' in TK-NOG mice is mature and functional. (2011)
  • Author(s): Hasegawa M, Kawai K, Mitsui T, Taniguchi K, Monnaoi M, Wakui M, Ito M,Suematsu M, Peltz G, Nakamura M, Suemizu1 M.
  • Journal Title: Biochem. Biophys. Res. Commun Volume: 405 (3) Pages: 405-410
  • Peer Reviewed
• [Journal Article] The influence of donor age on liver regeneration and hepatic progenitor cell populations. (2011)
  • Author(s): Ono Y, Kawachi S, Hayashida T, Wakui M, Tanabe M, Itano O, Obara H, Shinoda M, Hibi T, Oshima G, Tani N, Mihara K, Kitagawa Y.
  • Journal Title: Surgery. Volume: 150 (2) Pages: 154-161
  • Peer Reviewed
• [Journal Article] 質量分析によるがんの分子イメージング (2011)
  • Author(s): 涌井昌俊、久保亜紀子、大村光代、末松誠
  • Journal Title: 最新医学 Volume: 66 (10) Pages: 2321-2329
• [Journal Article] Semi-quantitative analyses of metabolic systems of human colon cancer metastatic xenografts in livers of superimmuno deficient NOG mice (2011)
  • Author(s): Kubo A
  • Journal Title: Analytical and Bioanalytical Chemistry Volume: 400 Pages: 1895-1904
  • Peer Reviewed
• [Journal Article] Development of imaging mass spectrometry (IMS) dataset extract software, IMS convolution (2011)
  • Author(s): Hayasaka T
  • Journal Title: Analytical and Bioanalytical Chemistry Volume: 401 Pages: 183-193
  • Peer Reviewed
• [Journal Article] 質量分析によるがんの分子イメージング (2011)
  • Author(s): 涌井昌俊
  • Journal Title: 最新医学 Volume: 66 Pages: 2321-2329
• [Journal Article] Semi-quantitative analyses of metabolic systems of human colon cancer metastatic xenografts in livers of superimmunodeficient NOG mice. (2011)
  • Author(s): Kubo A
  • Journal Title: Analytical and Bioanalytical Chemistry Volume: (印刷中)
  • Peer Reviewed
• [Journal Article] Reduced CD73 expression and its association with altered purine nucleotide metabolism in colorectal cancer cells robustly causing liver metastases. (2010)
  • Author(s): Matsuyama M, Wakui M, Monnai M, Mizushima T, Nishime C, Kawai K, Ohmura M, Suemizu H, Hishiki T, Suematsu M, Murata M, Chijiwa T, Furukawa D, OgoshiK, Makuuchi H, Nakamura M.
  • Journal Title: Oncol. Lett. Volume: 1 Pages: 431-436
  • Peer Reviewed
• [Journal Article] 生命科学・医学領域における質量分析イメージングの展開:臨床検査への応用の可能性. (2010)
  • Author(s): 涌井昌俊、久保亜紀子、末松誠、村田満
  • Journal Title: 日本臨床検査自動化学会会誌 Volume: 35 (3) Pages: 269-276
• [Journal Article] NOGマウスを用いたヒト化動物モデルの研究展開. (2010)
  • Author(s): 涌井昌俊、末水洋志.
  • Journal Title: 生化学 Volume: 82 (4) Pages: 314-318
  • NAID: 10026301245
• [Journal Article] Reduced CD73 expression and its association with altered purine nucleutide metabolism in colorectal cancer cells robustly causing liver metastases. (2010)
  • Author(s): Matsuyama M
  • Journal Title: Oncology Letters Volume: 1 Pages: 431-436
  • Peer Reviewed
• [Journal Article] 生命科学・医学領域における質量分析イメージングの展開:臨床検査への応用の可能性 (2010)
  • Author(s): 涌井昌俊
  • Journal Title: 日本臨床検査自動化学会会誌 Volume: 35 Pages: 269-276
• [Presentation] New software for imaging mass spectrometry data. (2012)
  • Author(s): MatsuuraM、Ushijima M, Yuba-KuboA,WakuiM, Hosaka K, Hayasaka T, Masaki N, Goto-Inoue N, Miyata S, Yao I, Setou M, Ogawa K, Kajihara S.
  • Organizer: Presented at the 103rd Annual Meeting of American Association for Cancer Research
  • Place of Presentation: Chicago Illinoi, USA
• [Presentation] New software for imaging mass spectrometry data. (2012)
  • Author(s): Matsuura M
  • Organizer: the 103rd Annual Meeting of American Association for Cancer Research
  • Place of Presentation: シカゴ（アメリカ）
• [Presentation] 質量顕微鏡とCE-MSを用いたヒト大腸がん肝転移モデルのin vivo flux解析の試み (2011)
  • Author(s): 久保亜紀子
  • Organizer: 第36回日本医用マススペクトル学会年会
  • Place of Presentation: ホテル阪急エキスポパーク(大阪府)
  • Year and Date: 2011-09-15
• [Presentation] 質量顕微鏡(MALDI-IT-TOFMS)とCE-MSを用いたヒト大腸ガン肝転移モデルの局所代謝解析 (2011)
  • Author(s): 久保亜紀子
  • Organizer: 第38回BMSコンファレンス(BMS2011)
  • Place of Presentation: 箱根高原ホテル(神奈川県)
  • Year and Date: 2011-07-10
• [Presentation] ヒト大腸ガンのIn vivo代謝を質量顕微鏡で観る (2011)
  • Author(s): 久保亜紀子
  • Organizer: 第63回日本細胞生物学会大会
  • Place of Presentation: 北海道大学(北海道)
  • Year and Date: 2011-06-27
• [Presentation] Semi-quantitative microscopic MALDI imaging for metabolites in human colon cancer-bearing livers of superimmunodeficient NOG mice (2011)
  • Author(s): Kubo A
  • Organizer: the 59^<th> American Society for Mass Spectrometry (ASMS) Conference on Mass Spectrometry and Allied Topics
  • Place of Presentation: 米国(デンバー)
  • Year and Date: 2011-06-05
• [Presentation] Software for peak picking using common peak method for imaging mass spectrometry data (2011)
  • Author(s): Ushijima M
  • Organizer: the 59^<th> American Society for Mass Spectrometry (ASMS) Conference on Mass Spectrometry and Allied Topics
  • Place of Presentation: 米国(デンバー)
  • Year and Date: 2011-06-05
• [Presentation] Semi-quantitative microscopic MALDI imaging formetabolites in human colon cancer-bearing livers of superimmunodeficient NOG mice. (2011)
  • Author(s): Kubo A, Ohmura M, Hishiki T, Wakui M, Kawai K, Nishime C, Murata M, Setou M, Suematsu M.
  • Organizer: the 59th American Society for Mass Spectrometry (ASMS) Conference on Mass Spectrometry and Allied Topics
  • Place of Presentation: Denver Colorado, USA
• [Presentation] Software for peak picking using common peak method for imaging mass spectrometry data. (2011)
  • Author(s): Ushijima M, Kajihara S, Hosaka K, Hayasaka T, Goto-Inoue N, Yuba-Kubo A, Wakui M, Yao I, Setou M, Matsuura M
  • Organizer: the 59th American Society for Mass Spectrometry (ASMS) Conference on Mass Spectrometry and Allied Topics
  • Place of Presentation: Denver Colorado, USA
• [Presentation] ヒト大腸ガンのIn vivo 代謝を質量顕微鏡で観る (2011)
  • Author(s): 久保亜紀子、大村光代、涌井昌俊、小 河 潔、瀬藤光利、末松 誠.
  • Organizer: 第63回日本細胞生物学会大会
  • Place of Presentation: 北海道
• [Presentation] 質量顕微鏡(MALDI-IT-TOFMS)とCE-MSを用いたヒト大腸ガン肝転移モデルの局所代謝解析. (2011)
  • Author(s): 久保亜紀子、大村光代、涌井昌俊、小 河 潔、瀬藤光利、末松 誠
  • Organizer: 第38回BMSコンファレンス (BMS2011)
  • Place of Presentation: 神奈川県
• [Presentation] イメージング質量分析に基づいて領域を判別するソフトウェアの開発. (2011)
  • Author(s): 牛嶋大、梶原茂樹、保坂蔵人、宮田敏、早坂孝宏、井上菜穂子、正木紀隆、久保亜紀子、涌井昌俊、矢尾育子、小河潔、瀬藤光利、松浦正明
  • Organizer: 第59回日本質量分析学会総合討論会
  • Place of Presentation: 大阪府
• [Presentation] 質量顕微鏡とCE-MS を用いたヒト大腸がん肝転移モデルのin vivo flux解析の試み. (2011)
  • Author(s): 久保亜紀子、大村光代、涌井昌俊、小 河 潔、瀬藤 光利、末松 誠
  • Organizer: 第36回日本医用マススペクトル学会年会
  • Place of Presentation: 大阪府
• [Presentation] 高分解能質量顕微鏡によるがん転移肝の代謝プロファイルの解明 (2010)
  • Author(s): 大村光代
  • Organizer: 第83回日本生化学会大会
  • Place of Presentation: 日本(神戸)
  • Year and Date: 2010-12-09
• [Presentation] Transporlal metastasis of human colon cancer impairs gluconeogenesis in superimmunodeficient NOG mice. (2010)
  • Author(s): Ohmura M
  • Organizer: The 9th World Congress for Microcirculation
  • Place of Presentation: フランス(パリ)
  • Year and Date: 2010-09-26
• [Presentation] 高分解能質量顕微鏡を用いたがん転移肝のエネルギー代謝変動の解明 (2010)
  • Author(s): 大村光代
  • Organizer: 第5回メタボロームシンポジウム
  • Place of Presentation: 日本(鶴岡)
  • Year and Date: 2010-09-11
• [Presentation] 質量顕微鏡とCE-MSによる担がん肝の局所代謝解析 (2010)
  • Author(s): 久保亜紀子
  • Organizer: 第35回日本医用マススペクトル学会年会
  • Place of Presentation: 日本(名古屋)(招待講演)
  • Year and Date: 2010-09-10
• [Presentation] Microscopic imaging mass spectrometry on hepatic micrometastasis of human colon cancer xenografts in superimmunodeficient NOG mice. (2010)
  • Author(s): Kubo A
  • Organizer: The 58^<th> American Society for mass Spectrometry (ASMS) Conference on Mass Spectrometry and Allied Topics
  • Place of Presentation: 米国(ソルトレイクシティ)
  • Year and Date: 2010-05-23
• [Presentation] Metaholnmic profiling of the liver bearing human colon cancer metastasis in superimmunodeficient NOG mice. (2010)
  • Author(s): Ohmura M
  • Organizer: Experimental Biology 2010
  • Place of Presentation: 米国(アナハイム)
  • Year and Date: 2010-04-24
• [Presentation] Reduced ecto-5'-nucleotidase CD73 expression and altered purine nucleotide metabolism in colorectal cancer cells robustly causing liver metastases. (2010)
  • Author(s): Malsuvama M
  • Organizer: The 100^<st> Annual Meeting of American Associstion for Cancer Research
  • Place of Presentation: 米国(ワシントンD.C.)
  • Year and Date: 2010-04-17
• [Presentation] Adaptation of cancer cells to hypoxic environments for tumor progression. (2010)
  • Author(s): Mizushima T
  • Organizer: The 100^<st> Annual Meeting of American Associstion for Cancer Research
  • Place of Presentation: 米国(ワシントンD.C.)
  • Year and Date: 2010-04-17
• [Presentation] Reduced ecto-5'-nucleotidase CD73 expression and altered purine nucleotide metabolism in colorectal cancer cells robustly causing liver metastases. (2010)
  • Author(s): Matsuyama M, Wakui M, Monnai M, Mizushima T, Nishime C, Kawai K, OhmuraM, Suemizu H, Hishiki T, Suematsu M, Murata M, Chijiwa T, Furukawa D^2, OgoshiK, Makuuchi H, Nakamura M.
  • Organizer: the 101st Annual Meeting of American Association for Cancer Research
  • Place of Presentation: Washington, DC, USA
• [Presentation] Adaptation of cancer cells to hypoxic environments for tumor progression. (2010)
  • Author(s): Mizushima T, Kawai K, Nishime C, OhmuraM, Hayakawa E, Matsuyama M, Asakura K, Izumi Y, Suemizu H, Ohnishi Y, NakamuraM, Suematsu M, Wakui M.
  • Organizer: the 101st Annual Meeting of American Association for Cancer Research
  • Place of Presentation: Washington, DC, USA
• [Presentation] Metabolomic profiling of the liver bearing human colon cancer metastasis in superimmunodeficient NOG mice. (2010)
  • Author(s): Ohmura M, Handa K, Nishime C, Mizushima T, Kawai K, Hishiki T, Yamamoto T, Wakui M, Suemizu H, Namakura M, Kiyagawa Y, Suematsu M.
  • Organizer: Experimental Biology 2010
  • Place of Presentation: Anaheim, California, USA
• [Presentation] A novel method to display the structural features included in the mass spectrometryimaging dataset. (2010)
  • Author(s): Yasuno M, Kajihara S, Morinaga H, Ikegami M, Ogawa K, Kubo A, Wakui M, Hayasaka T, Setou M.
  • Organizer: the 58th American Society for Mass Spectrometry (ASMS) Conference on Mass Spectrometry and Allied Topics
  • Place of Presentation: Salt Lake City, Utah, USA
• [Presentation] Microscopic imaging mass spectrometry on hepatic micrometastasis of human colon cancer xenografts in superimmunodeficient NOG mice (2010)
  • Author(s): Kubo A, Ohmura M, Wakui M, Kawai K, Nishime C, Hishiki T, Murata M, Ogawa K, Setou M, Suematsu M
  • Organizer: the 58th American Society for Mass Spectrometry (ASMS) Conference on Mass Spectrometry and Allied Topics
  • Place of Presentation: Salt Lake City, Utah, USA
• [Presentation] Transportal metastasis of human colon cancer impairs gluconeogenesis in superimmunodeficient NOG mice. (2010)
  • Author(s): Ohmura M, Kubo A, Handa K, Nishime C, Mizushima T, Kawai K, Hishiki T, Yamamoto T, Wakui M, Suemizu H, Nakamura M, Kitagawa Y, Setou M, Suematsu M.
  • Organizer: The 9th World Congress for Microcirculation
  • Place of Presentation: Paris, France
• [Presentation] Imaging Mass Spectrometryデータにおける構造解析ソフトの開発 (2010)
  • Author(s): 森永浩子、梶原茂樹、安野元英、池上将弘、小河潔、久保亜紀子、涌井昌俊、早坂孝宏、瀬藤光利
  • Organizer: 第58回日本質量分析学会総合討論会/第1回アジア・オセアニア質量分析会議
  • Place of Presentation: 茨城県
• [Presentation] 質量顕微鏡とCE-MSによる担がん肝の局所代謝解析. (2010)
  • Author(s): 久保亜紀子、大村光代、涌井昌俊、末松誠
  • Organizer: 第35回日本医用マススペクトル学会年会
  • Place of Presentation: 愛知県
• [Presentation] 高分解能質量顕微鏡を用いたがん転移肝のエネルギー代謝変動の解明. (2010)
  • Author(s): 大村光代、久保亜紀子、菱木貴子、川井健司、涌井昌俊、末水洋志、中村雅登、小河潔、瀬籐光利、末松誠.
  • Organizer: 第5回メタボロームシンポジウム
  • Place of Presentation: 山形県
• [Presentation] 高分解能質量顕微鏡によるがん転移肝の代謝プロファイルの解明 (2010)
  • Author(s): 大村光代、久保亜紀子、菱木貴子、川井健司、涌井昌俊、末水洋志、中村雅登、瀬藤光利、末松誠
  • Organizer: 第83回日本生化学会大会
  • Place of Presentation: 兵庫県
• [Patent(Industrial Property Rights)] 質量分析データ処理方法及び装置 (2012)
  • Inventor(s): 松浦 正明、牛嶋 大、涌井昌俊、瀬藤光利、梶原茂樹、小河 潔
  • Industrial Property Rights Holder: 公益財団法人がん研究会、株式会社島津製作所、国立大学法人浜松医科大学、学校法人慶應義塾
  • Industrial Property Number: 2012-102636
  • Filing Date: 2012-04-27
• [Patent(Industrial Property Rights)] MASS-ANALYSYS DATA PROCESSING METHOD AND SYSTEM (2012)
  • Inventor(s): Masaaki Matsuura, Masaru Ushijima, Masatoshi Wakui, Mitsutoshi Setou, Shigeki Kajihara, Kiyoshi Ogawa
  • Industrial Property Rights Holder: JAPANESE FOUNDATION FOR CANCER RESEARCH, SHIMADZU CORPORATION, National University Corporation Hamamatsu University Of Medicine, KEIO UNIVERSITY
  • Filing Date: 2012-04-27
  • Overseas
• [Patent(Industrial Property Rights)] MASS-ANALYSYS DATA PROCESSING METHOD AND SYSTEM (2012)
  • Inventor(s): 松浦 正明、牛嶋 大、涌井昌俊、瀬藤光利、梶原茂樹、小河 潔
  • Industrial Property Rights Holder: 公益財団法人がん研究会その他
  • Industrial Property Rights Type: 特許
  • Filing Date: 2012-04-27
  • Overseas