２光子励起顕微鏡を用いた大腸癌化及び癌、周囲間質応答の新規確証提示

• 研究課題/領域番号: 21390377
• 研究種目: 基盤研究(B)
• 配分区分: 補助金
• 応募区分: 一般
• 研究分野: 消化器外科学
• 研究機関: 三重大学
• 研究代表者: 楠 正人 三重大学, 医学(系)研究科(研究院), 教授 (50192026)
• 研究分担者: 井上 靖浩 三重大学, 医学部附属病院, 講師 (20324535) ; 三木 誓雄 三重大学, 大学院・医学系研究科, 客員教授 (50242962) ; 問山 裕二 三重大学, 大学院・医学系研究科, 助教 (00422824)
• 研究期間 (年度): 2009-04-01 – 2014-03-31
• 研究課題ステータス: 完了 (2013年度)
• 配分額: 12,480千円 (直接経費: 9,600千円、間接経費: 2,880千円); 2013年度: 520千円 (直接経費: 400千円、間接経費: 120千円); 2012年度: 1,040千円 (直接経費: 800千円、間接経費: 240千円); 2011年度: 1,040千円 (直接経費: 800千円、間接経費: 240千円); 2010年度: 1,820千円 (直接経費: 1,400千円、間接経費: 420千円); 2009年度: 8,060千円 (直接経費: 6,200千円、間接経費: 1,860千円)
• キーワード: 二光子レーザー顕微鏡 / 癌幹細胞 / 癌-間質反応 / 二光子励起顕微鏡 / 大腸癌 / 肝転移 / 上皮間葉移行 / 大陽癌

研究概要

大腸癌幹細胞が発癌過程または浸潤及び転移過程で周囲間質と相互作用をしながら進展していく様を二光励起顕微鏡で生体内可視化すること試みた。大腸癌肝転移モデルの早期では、癌細胞と肝類洞内皮細胞との接着及び停止、癌細細胞に胞血小板が付着するtumor cell induced platelet aggregation、癌細胞と白血球との相互作用が観察できた。後期では癌細胞塊と周囲間質及び腫瘍血管が観察できた。
RFP-HT29の5-FU抵抗性クローンは癌細胞の紡錘形変化と瀰漫性増殖への変化と周囲の著明な間質反応が確認できた。

研究成果

• [雑誌論文] Serum miR-200c is a novel prognostic and metastasis-predictive biomarker in patients with colorectal cancer (2014)
  • 著者名/発表者名: Toiyama Y, Hur K, Tanaka K, Inoue Y, Kusunoki M, Boland CR, Goel A
  • 雑誌名: Ann Surg 巻: 259(4) ページ: 735-743
  • 査読あり
• [雑誌論文] C-reactive protein as predictor of recurrence in patients with rectal cancer undergoing chemoradiotherapy followed by surgery (2013)
  • 著者名/発表者名: Toiyama Y, Inoue Y, Saigusa S, Kawamura M, Kawamoto A, Okugawa Y, Hiro J, Tanaka K, Mohri Y, Kusunoki M
  • 雑誌名: Anticancer Res 巻: 33(11) ページ: 5065-5074
  • 査読あり
• [雑誌論文] Multimodality therapy in fistula-associated perianal mucinous adenocarcinoma (2013)
  • 著者名/発表者名: Inoue Y, Kawamoto A, Okigami M, Okugawa Y, Hiro J, Toiyama Y, Tanaka K, Uchida K, Mohri Y, Kusunoki M
  • 雑誌名: Am Surg 巻: 79(9)
  • 査読あり
• [雑誌論文] Increased expression of Slug and Vimentin as novel predictive biomarkers for lymph node metastasis and poor prognosis in colorectal cancer (2013)
  • 著者名/発表者名: Toiyama Y, Yasuda H, Saigusa S, Tanaka K, Inoue Y, Goel A, Kusunoki M
  • 雑誌名: Carcinogenesis 巻: 34(11) ページ: 2548-2557
  • 査読あり
• [雑誌論文] Advances and directions in chemotherapy using implantable port systems for colorectal cancer : a historical review (2013)
  • 著者名/発表者名: Inoue Y, Kusunoki M
  • 雑誌名: Surg Today
  • 査読あり
• [雑誌論文] Leucine-rich repeat-containing G protein-coupled receptor 5 expression in ductular reactions after chemotherapy for metastatic colorectal cancer (2013)
  • 著者名/発表者名: Saigusa S, Tanaka K, Toiyama Y, Matsushita K, Kawamura M, Okugawa Y, Uchida K, Inoue Y, Mohri Y, Kusunoki M
  • 雑誌名: Hepatol Res 巻: 43(1) ページ: 84-90
  • NAID: 10031183461
  • 査読あり
• [雑誌論文] Intravital imaging of gastrointestinal diseases in preclinical models using two-photon laser scanning microscopy (2013)
  • 著者名/発表者名: Tanaka K, Toiyama Y, Inoue Y, Uchida K, Araki T, Mohri Y, Mizoguchi A, Kusunoki M
  • 雑誌名: Surg Today 巻: 43(2) ページ: 123-129
  • NAID: 10031167976
  • 査読あり
• [雑誌論文] Advances and directions in chemotherapy using implantable port systems for colorectal cancer: a historical review. (2013)
  • 著者名/発表者名: Inoue Y, Kusunoki M.
  • 雑誌名: Surg Today. 巻: Jul 28
  • 査読あり
• [雑誌論文] Increased expression of Slug and Vimentin as novel predictive biomarkers for lymph node metastasis and poor prognosis in colorectal cancer. (2013)
  • 著者名/発表者名: Toiyama Y, Yasuda H, Saigusa S, Tanaka K, Inoue Y, Goel A, Kusunoki M.
  • 雑誌名: Carcinogenesis. 巻: 34 号: 11 ページ: 2548-2557
  • DOI: 10.1093/carcin/bgt282
  • 査読あり
• [雑誌論文] Serum miR-21 as a diagnostic and prognostic biomarker in colorectal cancer. (2013)
  • 著者名/発表者名: Toiyama Y, Takahashi M, Hur K, Nagasaka T, Tanaka K, Inoue Y, Kusunoki M, Boland CR, Goel A.
  • 雑誌名: J Natl Cancer Inst. 巻: 105 号: 12 ページ: 849-859
  • DOI: 10.1093/jnci/djt101
  • 査読あり
• [雑誌論文] Intravital imaging of gastrointestinal diseases in preclinical models using two-photon laser scanning microscopy. (2013)
  • 著者名/発表者名: Tanaka K, Toiyama Y, Inoue Y, Uchida K, Araki T, Mohri Y, Mizoguchi A, Kusunoki M.
  • 雑誌名: Surg Today. 巻: 43 号: 2 ページ: 123-129
  • DOI: 10.1007/s00595-012-0283-9
  • NAID: 10031167976
  • 査読あり
• [雑誌論文] The preventive effects of low-dose enteric-coated aspirin tablets on the development of colorectal tumours in Asian patients: a randomised trial. (2013)
  • 著者名/発表者名: Ishikawa H, Mutoh M, Suzuki S, Tokudome S, Saida Y, Abe T, Okamura S, Tajika M, Joh T, Tanaka S, Kudo SE, Matsuda T, Iimuro M, Yukawa T, Takayama T, Sato Y, Lee K, Kitamura S, Mizuno M, Sano Y, Gondo N, Sugimoto K, Kusunoki M, Goto C, Matsuura N, Sakai T, Wakabayashi K.
  • 雑誌名: Gut. 巻: Jan 31 号: 11 ページ: 1755-1759
  • DOI: 10.1136/gutjnl-2013-305827
  • 査読あり
• [雑誌論文] Allelic Imbalance at an 8q24 Oncogenic SNP is Involved in Activating MYC in Human Colorectal Cancer. (2013)
  • 著者名/発表者名: Sugimachi K, Niida A, Yamamoto K, Shimamura T, Imoto S, Iinuma H, Shinden Y, Eguchi H, Sudo T, Watanabe M, Tanaka J, Kudo S, Hase K, Kusunoki M, Yamada K, Shimada Y, Sugihara K, Maehara Y, Miyano S, Mori M, Mimori K.
  • 雑誌名: Ann Surg Oncol. 巻: Jan 6.
• [雑誌論文] Clinical significance of LGR5 and CD44 expression in locally advanced rectal cancer after preoperative chemoradiotherapy (2012)
  • 著者名/発表者名: Saigusa S, Inoue Y, Tanaka K, Toiyama Y, Matsushita K, Kawamura M, Okugawa Y, Hiro J, Uchida K, Mohri Y, Kusunoki M
  • 雑誌名: Int J Oncol 巻: 41(5) ページ: 1643-4652
  • 査読あり
• [雑誌論文] In vivo real-time imaging of chemotherapy response on the liver metastatic tumor microenvironment using multiphoton microscopy (2012)
  • 著者名/発表者名: Tanaka K, Okigami M, Toiyama Y, Morimoto Y, Matsushita K, Kawamura M, Hashimoto K, Saigusa S, Okugawa Y, Inoue Y, Uchida K, Araki T, Mohri Y, Mizoguchi A, Kusunoki M
  • 雑誌名: Oncol Rep 巻: 28(5) ページ: 1822-1830
  • 査読あり
• [雑誌論文] High TrkB expression levels are associated with poor prognosis and EMT induction in colorectal cancer cells (2012)
  • 著者名/発表者名: Fujikawa H, Tanaka K, Toiyama Y, Saigusa S, Inoue Y, Uchida K, Kusunoki M
  • 雑誌名: J Gastroenterol 巻: 47(7) ページ: 775-784
  • NAID: 10030962144
  • 査読あり
• [雑誌論文] In vivo time-course imaging of tumor angiogenesis in colorectal liver metastases in the same living mice using two-photon laser scanning microscopy (2012)
  • 著者名/発表者名: Tanaka K, Morimoto Y, Toiyama Y, Matsushita K, Kawamura M, Koike Y, Okugawa Y, Inoue Y, Uchida K, Araki T, Mizoguchi A, Kusunoki M
  • 雑誌名: J Oncol 巻: 2012 ページ: 265487-265487
  • NAID: 120003596966
  • 査読あり
• [雑誌論文] Radiation induces epithelial-mesenchymal transition in colorectal cancer cells (2012)
  • 著者名/発表者名: Kawamoto A, Yokoe T, Tanaka K, Saigusa S, Toiyama Y, Yasuda H, Inoue Y, Miki C, Kusunoki M
  • 雑誌名: Oncol Rep 巻: 27(1) ページ: 51-57
  • 査読あり
• [雑誌論文] Intravital dual-colored visualization of colorectal liver metastasis in living mice using two photon laser scanning microscopy (2012)
  • 著者名/発表者名: Tanaka K, Morimoto Y, Toiyama Y, Okugawa Y, Inoue Y, Uchida K, Kimura K, Mizoguchi A, Kusunoki M
  • 雑誌名: Microsc Res Tech 巻: 75(3) ページ: 307-315
  • 査読あり
• [雑誌論文] In vivo real-time imaging of chemotherapy response on the liver metastatic tumor microenvironment using multiphoton microscopy. (2012)
  • 著者名/発表者名: Tanaka K et al.
  • 雑誌名: Oncol Rep. 巻: 28 号: 5 ページ: 1822-1830
  • DOI: 10.3892/or.2012.1983
  • 査読あり
• [雑誌論文] In vivo time-course imaging of tumor angiogenesis in colorectal liver me tastases in the same living mice using two-photon laser scanning microscopy (2012)
  • 著者名/発表者名: Tanaka K, Morimoto Y, Toiyama Y, Matsushita K, Kawamura M, Koike Y, Okugawa Y, Inoue Y, Uchida K, Araki T, Mizoguchi A, Kusunoki M
  • 雑誌名: J Oncol 巻: 2012 ページ: 265487-265487
  • NAID: 120003596966
  • 査読あり
• [雑誌論文] Cancer-associated fibroblasts correlate with poor prognosis in rectal cancer after chemoradiotherapy (2011)
  • 著者名/発表者名: Saigusa S, Toiyama Y, Tanaka K, Yokoe T, Okugawa Y, Fujikawa H, Matsusita K, Kawamura M, Inoue Y, Miki C, Kusunoki M
  • 雑誌名: Int J Oncol 巻: 38(3) ページ: 655-663
  • 査読あり
• [雑誌論文] CXCL5, a promoter of cell proliferation, migration and invasion, is a novel serum prognostic marker in patients with colorectal cancer (2011)
  • 著者名/発表者名: Kawamura M, Toiyama Y, Tanaka K, Saigusa S, Okugawa Y, Hiro J, Uchida K, Mohri Y, Inoue Y, Kusunoki M
  • 雑誌名: Eur J Cancer
  • 査読あり
• [雑誌論文] Intravital imaging of DSS-induced cecal mucosal damage in GFP-transgenic mice using two-photon microscopy. (2010)
  • 著者名/発表者名: Toiyama Y, Mizoguchi A, Okugawa Y, Koike Y, Morimoto Y, Araki T, Uchida K, Tanaka K, Nakashima H, Hibi M, Kimura K, Inoue Y, Miki C, Kusunoki M.
  • 雑誌名: J Gastroenterol. 巻: 45 ページ: 544-553
  • NAID: 120002777869
  • 査読あり
• [雑誌論文] Resection of rectal cancer : a historical review. (2010)
  • 著者名/発表者名: Inoue Y, Kusunoki M.
  • 雑誌名: Surg Today. 巻: 40 ページ: 501-506
  • NAID: 10027395844
  • 査読あり
• [雑誌論文] Loss of tumoral expression of soluble IL-6 receptor is associated with disease progression in colorectal cancer. (2010)
  • 著者名/発表者名: Okugawa Y, Miki C, Toiyama Y, Yasuda H, Yokoe T, Saigusa S, Hiro J, Tanaka K, Inoue Y, Kusunoki M.
  • 雑誌名: Br J Cancer. 巻: 103 ページ: 787-795
  • 査読あり
• [雑誌論文] Microdissection is essential for gene expression analysis of irradiated rectal canter tissues (2009)
  • 著者名/発表者名: Inoue Y, Tanaka K, Yokoe T, Saigusa S, Toiyama Y, Miki C, Kusunoki M.
  • 雑誌名: Oncol Rep. 22 ページ: 901-906
  • 査読あり
• [雑誌論文] Elevated CD133, but not VEGF or EGFR, as a predictive marker of distant recurrence after preoperative chemoradiotherapy in rectal cancer (2009)
  • 著者名/発表者名: Yasuda H, Tanaka K, Saigusa S, Toiyama Y, Koike Y, Okugawa Y, Yokoe T, Kawamoto A, Inoue Y, Miki C, Kusunoki M.
  • 雑誌名: Oncol Rep. 22 ページ: 709-717
  • 査読あり
• [雑誌論文] Correlation of CD133, OCT4, and SOX2 in rectal cancer and their association with distant recurrence after chemoradiotherapy (2009)
  • 著者名/発表者名: Saigusa S, Tanaka K, Toiyama Y, Yokoe T, Okugawa Y, Ioue Y, Miki C, Kusunoki M.
  • 雑誌名: Ann Surg Oncol. 16 ページ: 3488-3498
  • 査読あり
• [学会発表] Clinical significance of serum angiopoietin-like protein 2 in colorectal cancer patients (2014)
  • 著者名/発表者名: Takahito Kitajima, Yuji Toiyama, Tadanobu Shimura, Shozo Ide, Hiroki Imaoka, Satoru Kondo, Mikio Kawamura, Yoshinaga Okugawa, Aya Kawamoto, Junichiro Hiro, Susumu Saigusa, Masaki Ohi, Koji Tanaka, Yasuhiro Inoue, Yasuhiko Mohri, Masato Kusunoki
  • 学会等名: 2014 Gastrointestinal Cancers Symposium
  • 発表場所: San Francisco, CA, USA
• [学会発表] Serum angiopoietin-like protein 2 as a novel biomarker of diagnosis and prognosis in gastric cancer (2014)
  • 著者名/発表者名: Yuji Toiyama, Yasuhiro Inoue, Takahito Kitajima, Tadanobu Shimura, Hiroki Imaoka, Satoru Kondo, Shozo Ide, Masato Okigami, Hiromi Yasuda, Susumu Saigusa, Masaki Ohi, Koji Tanaka, Yasuhiko Mohri, Masato Kusunoki
  • 学会等名: 2014 Gastrointestinal Cancers Symposium
  • 発表場所: San Francisco, CA, USA
• [学会発表] The clinical significance of tissue miR-124 methylation in sporadic and ulcerative colitis-associated colorectal cancer (2013)
  • 著者名/発表者名: Yuji Toiyama, Keun Hur, Koji Tanaka, Yasuhiro Inoue, Takeshi Nagasaka, Masato Kusunoki, C. Richard Boland, Ajay Goel
  • 学会等名: AACR Annual Meeting 2013
  • 発表場所: Chicago, Illinois, USA
• [学会発表] Prognostic value of angiopoietin-like protein 2 (ANGPTL2) at the tumor margins in patients with gastric cancer (2013)
  • 著者名/発表者名: Tadanobu Shimura, Koji Tanaka, Susumu Saigusa, Satoru Kondo, Takahito Kitajima, Yuji Toiyama, Yoshinaga Okugawa, Yasuhiro Inoue, Toshimitsu Araki, Keiichi Uchida, Yasuhiko Mohri, Tsutomu Nobori, Masato Kusunoki
  • 学会等名: AACR Annual Meeting 2013
  • 発表場所: Chicago, Illinois, USA
• [学会発表] Expression of tropomyosin-related kinase B (TrkB) at the tumor invasive front as an independent prognostic factor in gastric cancer (2013)
  • 著者名/発表者名: Koji Tanaka, Tadanobu Shimura, Susumu Saigusa, Satoru Kondo, Takahito Kitajima, Yuji Toiyama, Yoshinaga Okugawa, Yasuhiro Inoue, Masaki Ohi, Toshimitsu Araki, Keiichi Uchida, Yasuhiko Mohri, Masato Kusunoki
  • 学会等名: AACR Annual Meeting 2013
  • 発表場所: Chicago, Illinois, USA
• [学会発表] Prognostic impact of Vasohibin 1 (VASH1) expression in tumor cells of colorectal cancer patients (2013)
  • 著者名/発表者名: Takahito Kitajima, Koji Tanaka, Susumu Saigusa, Tadanobu Shimura, Satoru Kondo, Yuji Toiyama, Yoshinaga Okugawa, Yasuhiro Inoue, Masaki Ohi, Toshimitsu Araki, Keiichi Uchida, Yasuhiko Mohri, Hiroki Hori, Masato Kusunoki
  • 学会等名: AACR Annual Meeting 2013
  • 発表場所: Chicago, Illinois, USA
• [学会発表] Aberrant expression of trefoil factor 3 (TFF3) is associated with tumor progression and an unfavorable prognosis in patients with colorectal cancer (2013)
  • 著者名/発表者名: Satoru Kondo, Koji Tanaka, Susumu Saigusa, Takahito Kitajima, Tadanobu Shimura, Yuji Toiyama, Yoshinaga Okugawa, Yasuhiro Inoue, Toshimitsu Araki, Keiichi Uchida, Yasuhiko Mohri, Kenichiro Ishii, Masato Kusunoki
  • 学会等名: AACR Annual Meeting 2013
  • 発表場所: Chicago, Illinois, USA
• [学会発表] Time-series assessment of 5-fluorouracil efficacy on murine colorectal liver metastasis model using intravital multiphoton microscopy (2012)
  • 著者名/発表者名: Tanaka K et al.
  • 学会等名: AACR Annual Meeting 2012
  • 発表場所: Chicago, Illinois
• [学会発表] Clinical and molecular comparison between short- and long-course preoperative radiotherapy for rectal cancer (2011)
  • 著者名/発表者名: Yasuhiro Inoue, Susumu Saigusa, Junichiro Hiro, Yuji Toiyama, Koji Tanaka, Yasuhiko Mohri, Masato Kusunoki
  • 学会等名: The 2011 ASCO Annual Meeting
  • 発表場所: Chicago, IL
• [学会発表] Macrophage inflammatory protein-3 alpha (MIP-3a) is a novel serum marker for prognosis of colorectal cancer (2010)
  • 著者名/発表者名: Takashi Iwata, Koji Tanaka, Yasuhiro Inoue, Yuji Toiyama, Junichiro Hiro, Susumu Saigusa, Yasuhiko Mohri, Chikao Miki, Tsutomu Tabata, Masato Kusunoki
  • 学会等名: 2010 ASCO Annual Meeting
  • 発表場所: CHICAGO, IL
• [学会発表] CD133, OCT4, and NANOG in ulcerative colitis-associated colorectal cancer (2009)
  • 著者名/発表者名: Tanaka K, Yasuda H, Okita Y, Araki T, Saigusa S, Toiyama Y, Yokoe T, Kawamoto A, Ioue Y, Miki C, Kusunoki M.
  • 学会等名: AACR 100th Annual Meeting 2009
  • 発表場所: Denver, CO, USA
  • 年月日: 2009-04-21
• [図書] Oncology Market Research Indicates Standardization of Colorectal Cancer Chemotherapy (2012)
  • 著者名/発表者名: Yasuhiro Inoue, Koji Tanaka, Masato Kusunoki
  • 出版者: Nova Publishers, New York
• [図書] The Role of Cytoreduction as a Multidisciplinary Treatment Modality for Metastatic Colorectal Cancer. (2010)
  • 著者名/発表者名: Koji Tanaka, Yasuhiro Inoue, Masato Kusunoki.
  • 出版者: Nova Publishers, New York
• [図書] PTMA (prothymosin, alpha) (2009)
  • 著者名/発表者名: Tanaka K, Kusunoki M.
  • 出版者: Atlas Genet Cytogenet Oncol Haematol
• [産業財産権] 個体内部の組織学的イメージ像を観察・取得する方法 (2013)
  • 発明者名: 溝口 明, 山口 輪作
  • 権利者名: 有限会社 楠屋
  • 取得年月日: 2013-05-17