Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
|
Outline of Final Research Achievements |
Cetuximab, a monoclonal antibody against the epidermal growth factor receptor, has been successfully applied in some patients with HNSCC. For effective treatment, it is essential to first identify Cetuximab-responsive patients. When we compared the expression of chemokine BRAK in HNSCC cells, both Cetuximab responsive HSC-3 and non-responsive YCU-H891 cells, we found expression of this chemokine only in the responsive HSC-3 cells. We also found that the promoter region of YCU-H891 cells were hyper methylated, and demethylation of this promoter recovered BRAK mRNA expression together with in vivo tumour-growth suppression by Cetuximab. Additionally, YCU-H891 cells were engineered to express BRAK in the presence of doxycycline in mice. Cetuximab-dependent tumour suppression was observed in vivo by doxycycline administration in the drinking water of the mice. These results indicate that BRAK expression would be a predictive biomarker for Cetuximab-dependent tumour suppression.
|