| Project/Area Number |
22591484
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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 | Mie University |
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Principal Investigator |
TANAKA Koji 三重大学, 医学部附属病院, 講師 (10345986)
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| Co-Investigator(Kenkyū-buntansha) |
INOUE Yasuhiro 三重大学, 医学部付属病院, 講師 (20324535)
MIKI Chikao 三重大学, 大学院・医学系研究科, 准教授 (50242962)
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) |
2010 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2012: ¥260,000 (Direct Cost: ¥200,000、Indirect Cost: ¥60,000)
Fiscal Year 2011: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2010: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
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| Keywords | 小腸大腸肛門外科学 / 直腸癌 / 化学放射線療法 / 癌幹細胞 / 上皮間葉移行 / 大腸癌 / 二光子レーザー顕微鏡 |
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| Research Abstract |
We hypothesized that residual cancer cells after chemoradiotherapy (CRT) for rectal cancer have the treatment (CRT)-resistant property and contain putative CSCs, compared with pre-CRT cancer specimens. Furthermore, residual cancer cells which survived CRT may acquire metastatic potential induced by EMT. The expression of CD133, leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), glucose transporter 1 (GLUT1), and hypoxia inducible factor-1α (HIF-1α) on residual cancer cells after CRT was associated with cancer recurrence and patient prognosis. The expression of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) on residual cancer cells after CRT was also associated with cancer recurrence. The expression of CXCR4 and its ligand CXCL12, fibroblast activation protein-α (FAP-α), and stromal cell-derived factor-1 (SDF-1) on the cancer stroma after CRT was also associated with cancer recurrence and patient prognosis. In vitro study, radiation induced EMT in colorectal cancer cells, resulting in the acquisition of invasive and metastatic properties. Neurotrophic receptor tropomyosin related kinase (TrkB) also induced EMT in colorectal cancer cells. TrkB was inversely correlated with E-cadherin, and associated with poor prognosis of colorectal cancer patients. CD133 was increased in a radiation dose-dependent manner, despite of the decreased number of clonogenic radiation-surviving cells.
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