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Morphological analysis of the mechanisms of organ-specific metastasis using intravital multiphoton microscopy

Research Project

Project/Area Number 23659646
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Digestive surgery
Research InstitutionMie University

Principal Investigator

MORIMOTO Yuhki  三重大学, 大学院・医学系研究科, リサーチアソシエイト (30586764)

Co-Investigator(Kenkyū-buntansha) TANAKA Koji  三重大学, 医学部附属病院, 講師 (10345986)
TOIYAMA Yuji  三重大学, 大学院・医学系研究科, 助教 (00422824)
INOUE Yasuhiro  三重大学, 医学部附属病院, 講師 (20324535)
MIZOGUCHI Akira  三重大学, 大学院・医学系研究科, 教授 (90181916)
KUSUNOKI Masato  三重大学, 大学院・医学系研究科, 教授 (50192026)
Project Period (FY) 2011 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2011: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords小腸大腸肛門外科学 / 癌臓器特異的転移 / 二光子レーザー顕微鏡 / 大腸癌 / 腫瘍-宿主相互作用 / 臓器特異的転移
Research Abstract

We visualized the interactions between cancer cells and stromal cells in tumor microenvironment with regard to ‘organ-specific metastasis, and in vivo real-time chemotherapy response for metastatic tumor xenografts using intravital TPLSM. Cancer cells were arrested within hepatic sinusoids after intrasplenic cancer cell injection. Platelet aggregation surrounding a cancer cell was observed, indicating a phenomenon of tumor-cell induced platelet aggregation (TCIPA). Cancer cells were extravasated from hepatic sinusoids to the space of Disse. Protrusions of Kupffer cells surrounding a cancer cell were observed, indicating that Kupffer cells appear to phagocytose cancer cells. After 5-fluorouracil (5-FU) or irinotecan chemotherapy, tumor cell fragmentation, condensation, swelling and intracellular vacuoles were observed. The platelet aggregation and the relatively decreased blood flow in the tumor vessels of colorectal liver metastases were also observed. 5-FU administration prior to the intrasplenic injection of cancer cells didn’t influence the adhesion of cancer cells to endothelial cells of hepatic sinusoids. We didn’t establish a liver metastasis model in subcutaneous tumor bearing mice because of the faster growth of subcutaneous tumor than liver metastatic tumor.

Report

(3 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Research-status Report
  • Research Products

    (33 results)

All 2013 2012 2011

All Journal Article (27 results) (of which Peer Reviewed: 27 results) Presentation (6 results) (of which Invited: 1 results)

  • [Journal Article] Leucine-rich repeat-containing G protein-coupled receptor 5 expression in ductular reactions after chemotherapy for metastatic colorectal cancer2013

    • Author(s)
      Saigusa S, Tanaka K, Toiyama Y, Matsushita K, Kawamura M, Okugawa Y, Uchida K, Inoue Y, Mohri Y, Kusunoki M
    • Journal Title

      Hepatol Res

      Volume: 43 Pages: 84-90

    • NAID

      10031183461

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Brain-derived neurotrophic factor/tropomyosin-related kinase B pathway in gastric cancer2013

    • Author(s)
      Okugawa Y, Tanaka K, Inoue Y, Kawamura M, Kawamoto A, Hiro J, Saigusa S, Toiyama Y, Ohi M, Uchida K, Mohri Y, Kusunoki M
    • Journal Title

      Br J Cancer

      Volume: 108 Pages: 121-30

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Smad interacting protein 1 (SIP1) is associated with peritoneal carcinomatosis in intestinal type gastric cancer2013

    • Author(s)
      Okugawa Y, Inoue Y, Tanaka K, Kawamura M, Saigusa S, Toiyama Y, Ohi M, Uchida K, Mohri Y, Kusunoki M
    • Journal Title

      Clin Exp Metastasis

      Volume: 30 Pages: 417-29

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Macrophage inflammatory protein-3 alpha (MIP-3a) is a novel serum prognostic marker in patients with colorectal cancer2013

    • Author(s)
      Iwata T, Tanaka K, Inoue Y, Toiyama Y, Hiro J, Fujikawa H, Okugawa Y, Uchida K, Mohri Y, Kusunoki M
    • Journal Title

      J Surg Oncol

      Volume: 107 Pages: 160-6

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Intravital imaging of gastrointestinal diseases in preclinical models using two-photon laser scanning microscopy2013

    • Author(s)
      Tanaka K, Toiyama Y, Inoue Y, Uchida K, Araki T, Mohri Y, Mizoguchi A, Kusunoki M
    • Journal Title

      Surg Today

      Volume: 43 Pages: 123-9

    • NAID

      10031167976

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Intravital imaging of gastrointestinal diseases in preclinical models using two-photon laser scanning microscopy.2013

    • Author(s)
      Tanaka K, Toiyama Y, Inoue Y, Uchida K, Araki T, Mohri Y, Mizoguchi A, Kusunoki M.
    • Journal Title

      Surg Today.

      Volume: 43 Issue: 2 Pages: 123-129

    • DOI

      10.1007/s00595-012-0283-9

    • NAID

      10031167976

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clinical significance of LGR5 and CD44 expression in locally advanced rectal cancer after preoperative chemoradiotherapy2012

    • Author(s)
      Saigusa S, Inoue Y, Tanaka K, Toiyama Y, Matsushita K, Kawamura M, Okugawa Y, Hiro J, Uchida K, Mohri Y, Kusunoki M
    • Journal Title

      Int J Oncol

      Volume: 41 Pages: 1643-52

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] In vivo real-time imaging of chemotherapy response on the liver metastatic tumor microenvironment using multiphoton microscopy2012

    • Author(s)
      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
    • Journal Title

      Oncol Rep

      Volume: 28 Pages: 1822-30

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Gene expression profiles of tumor regression grade in locally advanced rectal cancer after neoadjuvant chemoradiotherapy2012

    • Author(s)
      Saigusa S, Tanaka K, Toiyama Y, Matsushita K, Kawamura M, Okugawa Y, Hiro J, Inoue Y, Uchida K, Mohri Y, Kusunoki M
    • Journal Title

      Oncol Rep

      Volume: 28 Pages: 855-61

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] High TrkB expression levels are associated with poor prognosis and EMT induction in colorectal cancer cells2012

    • Author(s)
      Fujikawa H, Tanaka K, Toiyama Y, Saigusa S, Inoue Y, Uchida K, Kusunoki M
    • Journal Title

      J Gastroenterol

      Volume: 47 Pages: 775-84

    • NAID

      10030962144

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Okugawa Y, Toiyama Y, Inoue Y, Iwata T, Fujikawa H, Saigusa S, Konishi N, Tanaka K, Uchida K, Kusunoki M2012

    • Author(s)
      Okugawa Y, Toiyama Y, Inoue Y, Iwata T, Fujikawa H, Saigusa S, Konishi N, Tanaka K, Uchida K, Kusunoki M
    • Journal Title

      J Surg Res

      Volume: 175

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] CXCL5, a promoter of cell proliferation, migration and invasion, is a novel serum prognostic marker in patients with colorectal cancer2012

    • Author(s)
      Kawamura M, Toiyama Y, Tanaka K, Saigusa S, Okugawa Y, Hiro J, Uchida K, Mohri Y, Inoue Y, Kusunoki M
    • Journal Title

      Eur J Cancer

      Volume: 48 Pages: 2244-51

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] In vivo time-course imaging of tumor angiogenesis in colorectal liver metastases in the same living mice using two-photon laser scanning microscopy2012

    • Author(s)
      Tanaka K, Morimoto Y, Toiyama Y, Matsushita K, Kawamura M, Koike Y, Okugawa Y, Inoue Y, Uchida K, Araki T, Mizoguchi A, Kusunoki M
    • Journal Title

      J Oncol

      Volume: 2012 Pages: 265487-265487

    • NAID

      120003596966

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Evaluation of CXCL10 as a novel serum marker for predicting liver metastasis and prognosis in colorectal cancer2012

    • Author(s)
      Toiyama Y, Fujikawa H, Kawamura M, Matsushita K, Saigusa S, Tanaka K, Inoue Y, Uchida K, Mohri Y, Kusunoki M
    • Journal Title

      Int J Oncol

      Volume: 40 Pages: 560-6

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] TS and DPD mRNA levels on formalin-fixed paraffin-embedded specimens as predictors for distant recurrence of rectal cancer treated with preoperative chemoradiotherapy2012

    • Author(s)
      Tanaka K, Saigusa S, Toiyama Y, Koike Y, Okugawa Y, Yokoe T, Inoue Y, Kobayashi M, Miki C, Kusunoki M
    • Journal Title

      J Surg Oncol

      Volume: 105 Pages: 529-34

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Radiation induces epithelial-mesenchymal transition in colorectal cancer cells2012

    • Author(s)
      Kawamoto A, Yokoe T, Tanaka K, Saigusa S, Toiyama Y, Yasuda H, Inoue Y, Miki C, Kusunoki M
    • Journal Title

      Oncol Rep

      Volume: 27 Pages: 51-7

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Inhibition of HGF/cMET expression prevents distant recurrence of rectal cancer after preoperative chemoradiotherapy2012

    • Author(s)
      Saigusa S, Toiyama Y, Tanaka K, Yokoe T, Fujikawa H, Matsushita K, Okugawa Y, Inoue Y, Uchida K, Mohri Y, Kusunoki M
    • Journal Title

      Int J Oncol

      Volume: 40 Pages: 583-91

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Soluble CXCL16 in preoperative serum is a novel prognostic marker and predicts recurrence of liver metastases in colorectal cancer patients2012

    • Author(s)
      Matsushita K, Toiyama Y, Tanaka K, Saigusa S, Hiro J, Uchida K, Inoue Y, Kusunoki M
    • Journal Title

      Ann Surg Oncol

      Volume: 19

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Intravital dual-colored visualization of colorectal liver metastasis in living mice using two photon laser scanning microscopy2012

    • Author(s)
      Tanaka K, Morimoto Y, Toiyama Y, Okugawa Y, Inoue Y, Uchida K, Kimura K, Mizoguchi A, Kusunoki M
    • Journal Title

      Microsc Res Tech

      Volume: 75 Pages: 307-15

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Clinical significance of radiation-induced CD133 expression in residual rectal cancer cells after chemoradiotherapy2012

    • Author(s)
      Kawamoto A, Tanaka K, Saigusa S, Toiyama Y, Morimoto Y, Fujikawa H, Iwata T, Matsushita K, Yokoe T, Yasuda H, Inoue Y, Miki C, Kusunoki M
    • Journal Title

      Exp Ther Med

      Volume: 3(3) Pages: 403-409

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] In vivo real-time imaging of chemotherapy response on the liver metastatic tumor microenvironment using multiphoton microscopy.2012

    • Author(s)
      Tanaka K et al.
    • Journal Title

      Oncol Rep.

      Volume: 28 Issue: 5 Pages: 1822-1830

    • DOI

      10.3892/or.2012.1983

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Intravital three-dimensional dynamic pathology of experimental colitis in living mice using two-photon laser scanning microscopy2011

    • Author(s)
      Morimoto Y, Tanaka K, Toiyama Y, Inoue Y, Araki T, Uchida K, Kimura K, Mizoguchi A, Kusunoki M
    • Journal Title

      J Gastrointest Surg

      Volume: 15 Pages: 1842-50

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] In vivo real-time two-photon microscopic imaging of platelet aggregation induced by selective laser irradiation to the endothelium created in the beta-actin-green fluorescent protein transgenic mice2011

    • Author(s)
      Koike Y, Tanaka K, Okugawa Y, Morimoto Y, Toiyama Y, Uchida K, Miki C, Mizoguchi A, Kusunoki M
    • Journal Title

      J Thromb Thrombolysis

      Volume: 32 Pages: 138-45

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cancer-associated fibroblasts correlate with poor prognosis in rectal cancer after chemoradiotherapy2011

    • Author(s)
      Saigusa S, Toiyama Y, Tanaka K, Yokoe T, Okugawa Y, Fujikawa H, Matsusita K, Kawamura M, Inoue Y, Miki C, Kusunoki M
    • Journal Title

      Int J Oncol

      Volume: 38 Pages: 655-63

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Evaluation of an inflammation-based prognostic score for the identification of patients requiring postoperative adjuvant chemotherapy for stage II colorectal cancer2011

    • Author(s)
      Toiyama Y, Miki C, Inoue Y, Tanaka K, Mohri Y, Kusunoki M
    • Journal Title

      Exp Ther Med

      Volume: 2 Pages: 95-101

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Clinical significance of CD133 and hypoxia inducible factor-1α gene expression in rectal cancer after preoperative chemoradiotherapy2011

    • Author(s)
      Saigusa S, Tanaka K, Toiyama Y, Yokoe T, Okugawa Y, Koike Y, Fujikawa H, Inoue Y, Miki C, Kusunoki M
    • Journal Title

      Clin Oncol (R Coll Radiol)

      Volume: 23 Pages: 323-32

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Intravital three-dimensional dynamic pathology of experimental colitis in living mice using two-photon laser scanning microscopy.2011

    • Author(s)
      Morimoto Y, Tanaka K, Toiyama Y, Inoue Y, Araki T, Uchida K, Kimura K, Mizoguchi A, Kusunoki M.
    • Journal Title

      J Gastrointest Surg.

      Volume: 15 Pages: 1842-1850

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] Intravital assessment of infliximab efficacy in murine ulcerative colitis model using two photon laser scanning microscopy (P-76)2012

    • Author(s)
      Kohei Matsushita, Koji Tanaka, Yuhki Morimoto, Masato Okigami, Mikio Kawamura, Kiyosi Hashimoto, Susumu Saigusa, Yuji Toiyama, Yuuki Koike, Yoshinaga Okugawa, Yasuhiro Inoue, Toshimitsu Araki, Keiichi Uchida, Yasuhiko Mohri, Akira Mizoguchi, and Masato Kusunoki
    • Organizer
      The 6th Korea-Japan IBD Symposium
    • Place of Presentation
      Keio Plaza Hotel Tokyo
    • Year and Date
      2012-01-28
    • Related Report
      2012 Final Research Report
  • [Presentation] Time-series assessment of 5-fluorouracil efficacy on murine colorectal liver metastasis model using intravital multiphoton microscopy (2432)2012

    • Author(s)
      Koji Tanaka, Masato Okigami, Yuhki Morimoto, Kohei Matsushita, Mikio Kawamura, Kiyoshi Hashimoto, Yuji Toiyama, Susumu Saigusa, Yoshinaga Okugawa, Yuhki Koike, Yasuhiro Inoue, Toshimitsu Araki, Keiichi Uchida, Yasuhiko Mohri, Akira Mizoguchi, Masato Kusunoki.
    • Organizer
      AACR 103rdAnnual Meeting
    • Place of Presentation
      Chicago Illinois
    • Related Report
      2012 Final Research Report
  • [Presentation] In vivo real-time imaging of tumor microcirculatory alterations in colorectal liver metastatic xenografts by chemotherapy using multiphoton microscopy. J Clin Oncol 30, 2012 (suppl; abstr e21053)2012

    • Author(s)
      Koji Tanaka, Masato Okigami, Yuji Toiyama, Yuhki Morimoto, Kohei Matsushita, Mikio Kawamura, Kiyoshi Hashimoto, Susumu Saigusa, Yoshinaga Okugawa, Junichiro Hiro, Yasuhiro Inoue, Keiichi Uchida, Toshimitsu Araki, Yasuhiko Mohri, Akira Mizoguchi, Masato Kusunoki
    • Organizer
      2012 ASCO Annual Meeting
    • Place of Presentation
      Chicago, Illinois
    • Related Report
      2012 Final Research Report
  • [Presentation] Time-series assessment of 5-fluorouracil efficacy on murine colorectal liver metastasis model using intravital multiphoton microscopy2012

    • Author(s)
      Koji Tanaka et al
    • Organizer
      AACR Annual Meeting 2012
    • Place of Presentation
      Chicago, Illinois
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] Intravital dual-colored visualization of colorectal liver metastasis formation in the living mice using two photon laser scanning microscopy (5278)2011

    • Author(s)
      Koji Tanaka, Yuhki Morimoto, Kohei Matsushita, Mikio Kawamura, Yuji Toiyama, Susumu Saigusa, Yoshinaga Okugawa, Yuhki Koike, Yasuhiro Inoue, Chikao Miki, Akira Mizoguchi, Masato Kusunoki.
    • Organizer
      AACR 102ndAnnual Meeting 2011
    • Place of Presentation
      Orlando, Florida
    • Related Report
      2012 Final Research Report
  • [Presentation] Intravital evaluation of time-course efficacy of anticancer drugs on colorectal liver metastases in the same living mice using two-photon laser scanning microscopy. J Clin Oncol 29: 2011 (suppl; abstr 10621)2011

    • Author(s)
      K. Tanaka, Y. Morimoto, Y. Toiyama, S. Saigusa, Y. Okugawa, Y. Inoue, K. Uchida, K. Matsushita, M. Kawamura, A. Mizoguchi, M. Kusunoki
    • Organizer
      2011 ASCO Annual Meeting
    • Place of Presentation
      Chicago, Illinois
    • Related Report
      2012 Final Research Report

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Published: 2011-08-05   Modified: 2019-07-29  

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