Morphological analysis of the mechanisms of organ-specific metastasis using intravital multiphoton microscopy
Project/Area Number |
23659646
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Research Category |
Grant-in-Aid for Challenging Exploratory Research
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Allocation Type | Multi-year Fund |
Research Field |
Digestive surgery
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Research Institution | Mie 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)
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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)
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Project Period (FY) |
2011 – 2012
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Project Status |
Completed (Fiscal Year 2012)
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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)
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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.
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Report
(3 results)
Research Products
(33 results)
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[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
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Journal Title
Br J Cancer
Volume: 108
Pages: 121-30
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[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
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Journal Title
Int J Oncol
Volume: 41
Pages: 1643-52
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[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
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Journal Title
Oncol Rep
Volume: 28
Pages: 1822-30
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Peer Reviewed
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[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
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Journal Title
Oncol Rep
Volume: 28
Pages: 855-61
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Peer Reviewed
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[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
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Journal Title
Related Report
Peer Reviewed
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[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
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Journal Title
Eur J Cancer
Volume: 48
Pages: 2244-51
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Peer Reviewed
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[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
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Journal Title
J Oncol
Volume: 2012
Pages: 265487-265487
NAID
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Peer Reviewed
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[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
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Journal Title
Int J Oncol
Volume: 40
Pages: 583-91
Related Report
Peer Reviewed
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[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
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Journal Title
Exp Ther Med
Volume: 3(3)
Pages: 403-409
Related Report
Peer Reviewed
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[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
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Journal Title
Int J Oncol
Volume: 38
Pages: 655-63
Related Report
Peer Reviewed
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[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
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[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
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[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
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[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
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[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
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