| Budget Amount *help |
¥48,100,000 (Direct Cost: ¥37,000,000、Indirect Cost: ¥11,100,000)
Fiscal Year 2009: ¥14,300,000 (Direct Cost: ¥11,000,000、Indirect Cost: ¥3,300,000)
Fiscal Year 2008: ¥14,950,000 (Direct Cost: ¥11,500,000、Indirect Cost: ¥3,450,000)
Fiscal Year 2007: ¥18,850,000 (Direct Cost: ¥14,500,000、Indirect Cost: ¥4,350,000)
|
|---|
| Research Abstract |
(1) HUVEC clones resistant to VEGFR2-TKI Ki8751 exhibited the downregulation of VEGFR2, a decreased signal response to VEGF stimulation, and the loss of vascular endothelial markers. These results strongly suggest that an escape from VEGFR2 signaling-dependency is one of the mechanisms of resistance to VEGFR2-TKI in vascular endothelial cells.
(2) We identified VEGFR2+pTyr+ peripheral blood Leukocytes as a feasible and non-invasive pharmacodynamic biomarker in vivo. Our findings suggest the clinical utility of VEGFR2+pTyr+ PBLs as a VEGF signal-specific biomarker of VEGFR2 tyrosine kinase inhibitors for use in early clinical trials.
(3) Phase I clinical and biomarker study demonstrated that BIBF 1120-treatment significantly increased percentage of CD133+CD117-cells (p<0.001) on Day 29 compared with pre-treatment, and conversely decreased that of CD133-CD117+ cells (p<0.01). Our biomarker data provide a novel insight into CD133 and CD117 positive cells as a potential pharmacodynamic biomarker for an anti-angiogenic inhibitor.
|
