| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2017: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
|
|---|
| Outline of Final Research Achievements |
We previously reported on VHL mutations in malignant pleural mesothelioma (MPM) patients’ samples. Here we conduct in vitro study to access the therapeutic approaches in VHL-mutant MPM. MPM cell lines with or without VHL mutation were used in this study. Molecular targeted agents were tested for growth-inhibitory effect and the effects of HIF-1α knockdown by siRNA were also evaluated in these cell lines.
NCI-H28 MPM cells harboring VHL L89H mutation were sensitive to YC-1, known as a hypoxia inducible factor (HIF)-1α inhibitor, and YC-1 treatment induced massive apoptosis. YC-1 had no effect in the other MPM cells without VHL mutations. Knockdown of HIF-1α by siRNA partially inhibited the growth of NCI-H28 cells, suggesting additional blockade may be required for complete shutdown of growth signaling. Further investigation is necessary to detect other molecules relevant to VHL-HIF pathway for the development of better therapeutic approaches.
|
