| Project/Area Number |
24650643
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Clinical oncology
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| Research Institution | Tohoku University |
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Principal Investigator |
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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 |
¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 腫瘍血流遮断 / コンブレタスタチン / 腫瘍血管 / EPR効果 / 高分子ミセル / DDS / インターフェイス / 癌 |
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| Outline of Final Research Achievements |
Nanoparticles are difficult to extravasate from initial stage tumor vessels. Therefore, enhanced-permeability and retention (EPR) effects do not occur in such vessels. A combretastatin derivative, Cderiv, enhances vascular permeability. To elucidate the microcirculation mechanisms of the EPR effect, we investigated the structure and function of tumor vessels and tumor-host interface (T-HI) vessels after Cderiv administration. We also assessed the therapeutic enhancement effects of the combination of doxorubicin micelle with Cderiv. Results show the following. (1) The T-HI vessel endothelium contained many vesiculo-vacuolar organelles (VVO), which contribute to macromolecule extravasation, even after the Cderiv administration. (2) Combination therapy (Cderiv + doxorubicin micelle) markedly inhibited LY80 tumor growth. The presence of VVO and the decline of tumor microcirculation function involving T-HI are important for the EPR effect.
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