| Project/Area Number |
18591495
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | Shizuoka Cancer Center |
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Principal Investigator |
KAWAMURA Taiichi (2007) Shizuoka Cancer Center, Research Institute, Researcher (20283145)
米村 豊 (2006) 静岡県立静岡がんセンター(研究所), 研究員 (20167042)
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| Co-Investigator(Kenkyū-buntansha) |
ENDO Yoshio Kanzawa Univ., Cancer Research Institute, Associate Professor (30211783)
OHSHIMA Keiichi Shizuoka Cancer Center, Research Institute, Researcher (10399587)
BANDO Etsuro Shizuoka Cancer Center, Research Institute, Researcher (70399591)
MOCHIZUKI Toru Shizuoka Cancer Center, Research Institute, Researcher (00117780)
ITO HIROAKI Shizuoka Cancer Center, Research Institute, Researcher (70443447)
川村 泰一 静岡県立静岡がんセンター(研究所), 研究員 (20283145)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,750,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥450,000)
Fiscal Year 2007: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | peritoneal dissemination / 腹膜中皮 / VEGF-C / 腹腔内遊離がん細胞 / リンパ管新生 / 血管新生 / MMP-7 |
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| Research Abstract |
Origin of peritoneal carcinomatsis is considered from peritoneal free cancer cells exfoliated from serosal surface of the primary tumor or spilled from the blood vessels/lymphatic vessels during the surgical dissection. These peritoneal free cancer cells have high proliferative activity of greater than 50% of Ki67-labeling rate, measured by MIB-1 monoclonal antibody. Accordingly, peritoneal free cancer cells start to proliferate immediately if they attach on the peritoneal surface. By the scanning electromicroscopy, some kinds of cytokines induce morphological changes of peritoneal mesothelial cells. EGF, IL-6 and hGF induce contraction of peritoneal mesothelial cells, and then submesothelial basement membrane and the orifice of submesthelial lymphatic vessels are exposed.
A new cascade of peritoneal metastasis, called as trans-lymphatic metastasis is studied. The lymphatics and blood vessels in the human peritoneum with peritoneal carcinomatosis were studied using by the method of 5'-N
… More
ase-ALPase and D2-40 immunostatining. Cancer cells are found in the submesothelial lymphatic vessels in the milky spots, diaphragmatic lymphatics and the initial lymphatics in the pelvis and Morrison pouch. In the milky spots, many arterial blood capillaries distribute around the lymphatic sinus. Dilatation and newly formed lymphatic vessels were found, and are classified into four patterns, like budding, ladder formation, etension and island formation. High levels of VEGF-C and VEGF-A were detected in the ascites. VEGF-C has a role in the formation of lymphangiogenesis.
From these results, peritoneal free cancer cells migrate into the submesothelial lymphatic vessels. Accordingly, trans-lymphatic metastasis is an important metastatic process on the formation of peritoneal dissemination, and VEGF-C has a big role in the neoformation of submesothelial lymphatic vessels.
A new surgical method called peritonectomy is the surgical procedure to remove peritoneal zones with well developed lymphatic networks, and enables to perform complete removal of PC. Furthermore, intraperitoneal chemotherapy effectively kills cancer cells in the submesothelial lymphatics by making a high locoregional concentrations of anticancer drugs. Less
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