| Budget Amount *help |
¥180,180,000 (Direct Cost: ¥138,600,000、Indirect Cost: ¥41,580,000)
Fiscal Year 2014: ¥33,150,000 (Direct Cost: ¥25,500,000、Indirect Cost: ¥7,650,000)
Fiscal Year 2013: ¥34,580,000 (Direct Cost: ¥26,600,000、Indirect Cost: ¥7,980,000)
Fiscal Year 2012: ¥36,270,000 (Direct Cost: ¥27,900,000、Indirect Cost: ¥8,370,000)
Fiscal Year 2011: ¥35,880,000 (Direct Cost: ¥27,600,000、Indirect Cost: ¥8,280,000)
Fiscal Year 2010: ¥40,300,000 (Direct Cost: ¥31,000,000、Indirect Cost: ¥9,300,000)
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| Outline of Final Research Achievements |
In terms of malignant transformation in cancer cells, interaction of cancer stem cells with endothelial cells or myofibroblasts as tumor microenvironmental cells was analyzed. As a result, when tumor vasculature was focused, we found that cancer stem cells existing near myofibroblasts abundantly localizing at perivascular area show drug resistance. To assess this phenomenon, we established tumor myofibroblasts cell line and analyzed the up-regulating genes in myofibroblasts upon exposure with hypoxia and/or serum starvation. In this treatment, we identified that CD44 is up-regulated under the hypoxia and this molecule supports stemness of cancer stem cells and induces drug resistance of cancer cells. In order to improve the tissue hypoxia in the tumor microenvironment, it is required to normalize very leaky and immature tumor vasculature. In this experiment, we found that apelin normalizes tumor vasculature, resulting in improvement of drug delivery and tumor immunity.
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