| Project/Area Number |
23390198
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | The University of Tokushima |
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Principal Investigator |
KONDO Shigetada 徳島大学, ヘルスバイオサイエンス研究部, 准教授 (40304513)
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| Co-Investigator(Renkei-kenkyūsha) |
KUWANO Yuki 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 助教 (00563454)
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| Project Period (FY) |
2011-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥19,370,000 (Direct Cost: ¥14,900,000、Indirect Cost: ¥4,470,000)
Fiscal Year 2013: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2012: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2011: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
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| Keywords | 血管新生阻害 / VEGF / FGF２ / ノンコーディングRNA / 悪性進展 / 機能性ＲＮＡ / 腫瘍血管新生 / FGF-2 / FGF2 / non-coding RNA / がん / 機能性RNA / 悪性腫瘍化 |
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| Research Abstract |
VEGF-targeted therapies have become an important treatment for a number of human malignancies. The VEGF inhibitors are actually effective in several types of cancers, however, the benefits are transiently, and the vast majority of patients who initially respond to the therapies will develop resistance.
I elucidate that one of mechanisms for the acquired resistance is the direct effect(s) of VEGF inhibitors on tumor cells expressing VEGF receptors. Treatment with bevacizumab and 5-FU induced two novel non-coding (nc)RNAs. These ncRNAs silenced p53 expression and inhibited p53 function. As the results, these ncRNAs induced malignant phenotypes in colon cancer cells, including over-activation of HIF1, angiogenic switching, resistance of apoptosis, aberrant cell cycle regulation, cancer stem-like phenotype, and resistance to bevacizumab. I revealed expression profiles of these ncRNAs in colon cancer patients; these ncRNA was overexpressed in patients treated with bevacizumab.
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