| Project/Area Number |
24390312
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | Hamamatsu University School of Medicine |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
KAMIYA Kinji 浜松医科大学, 医学部附属病院, 講師 (20324361)
OHTA Manabu 浜松医科大学, 医学部附属病院, 講師 (40397394)
KIKUCHI Hirotoshi 浜松医科大学, 医学部, 助教 (70397389)
MIYAZAKI Shinichiro 浜松医科大学, 医学部附属病院, 医員 (30571575)
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| Co-Investigator(Renkei-kenkyūsha) |
BABA Satoshi 浜松医科大学, 医学部附属病院, 准教授 (10242760)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥18,330,000 (Direct Cost: ¥14,100,000、Indirect Cost: ¥4,230,000)
Fiscal Year 2014: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Fiscal Year 2013: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2012: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
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| Keywords | 抗血管新生治療 / 大腸癌 / 腫瘍微小環境 / 低酸素 / 癌悪性化 / 治療抵抗性 / 癌微小環境 / 癌幹細胞 / 分子標的治療 |
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| Outline of Final Research Achievements |
Bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor (VEGF)-A has been used for colorectal cancer treatment. However, a number of preclinical reports indicate the development of resistance to anti-angiogenic therapy. In this study, we addressed the effects of anti-VEGF antibodies on the growth and malignant behavior of colorectal cancer cells using an orthotopic implantation model of TK-4, a solid tumor strain derived from a colon cancer patient, into nude mice. Intratumoral hypoxia induced by anti-VEGF antibody treatment resulted in induction of stanniocalcin 2 (STC2), a target gene of hypoxia inducible factor-1 (HIF-1), to enhance colon cancer cell growth and migration. Our data provide a potential molecular explanation for the limited clinical effectiveness of anti-VEGF antibodies and rebound phenomenon after withdrawal of bevacizumab.
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