| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Outline of Final Research Achievements |
A tyrosine kinase inhibitor imatinib is known to be effective for gastrointestinal stromal tumors (GISTs), a hallmark of which is a constitutive activation of KIT tyrosine kinase by c-kit gene mutation. In order to overcome imatinib resistance in GISTs, imatinib-resistant GISTs were compared with imatinib-naive GISTs as follows in the present investigation. 5-hydroxymethylcytosine was immunohistochemically shown to be globally decreased in imatinib-resistant GISTs as well as in high-risk imatinib-naive GISTs, compared with low-risk imatinib-naive GISTs. On the other hand, in contrast to imatinib-naive GISTs, endothelial induction of PD-L1 was observed in both in and outside of imatinib-resistant GISTs. Imatinib-resistance of GISTs seems to be rather associated with endothelial expression of PD-L1 than global epigenetic change such as decrease in 5hmc. This may be a rational for PD-L1 therapy in order to overcome imatinib resistance of GISTs.
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