| Project/Area Number |
18K16798
|
|---|
| Research Category |
Grant-in-Aid for Early-Career Scientists
|
| Allocation Type | Multi-year Fund |
|---|
| Review Section |
Basic Section 56040:Obstetrics and gynecology-related
|
|---|
| Research Institution | Osaka University |
|---|
Principal Investigator |
Nakatsuka Erika 大阪大学, 医学系研究科, 特任助教(常勤) (00816514)
|
|---|
| Project Period (FY) |
2018-04-01 – 2020-03-31
|
| Project Status |
Completed (Fiscal Year 2019)
|
| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
|
|---|
| Keywords | 卵巣癌 / ベバシズマブ耐性 / PAI-1 / microRNA / 血管新生 / ベバシズマブ / マイクロRNA / VEGF / 血管新生因子 |
|---|
| Outline of Final Research Achievements |
Bevacizumab plays a key role in ovarian cancer treatment; however, the bevacizumab resistance is often seen in clinical setting. The aim of this study is to identify miRNAs which are involved in bevacizumab resistance. ID-8 cancer cells were injected i.p. into C57BL/6 mice, and anti-VEGF IgG and control IgG were treated twice weekly. Thereafter, mice were sacrificed, and RNA extracted from tumor. MiRNA microarray and TaqMan Gene Expression assays were performed to identify miRNAs/genes which are related with bevacizumab resistance. Through miRNA microarray, 3 miRNAs (miR-30b-5p, 143-3p and 192-5p) were found to be down-regulated by bevacizumab and TaqMan assays showed SERPINE1/PAI-1 elevated. In public database, patients with high PAI-1 expression were correlated with worse prognosis. Transducing these miRNAs downregulated PAI-1 expression in cancer cells. The data presented may explain the mechanism of bevacizumab resistance, suggesting their potential as treatment targets.
|
| Academic Significance and Societal Importance of the Research Achievements |
卵巣癌において血管新生は極めて重要である。しかしながら、血管新生因子VEGF に対する抗体であるベバシズマブ (Bev) の臨床への導入にも関わらず、いまだ抜本的な生存率の改善を認めていない。今回の研究の目的は卵巣がん患者がBev抗性を獲得するメカニズムの解明であり、最終的には進行卵巣がんにおける BEV 耐性化症例対する新治療の可能性の提示につながる基礎データの創出することである。治療法が進化した現在でも卵巣癌は患者の約半数が死亡する致死的な疾患であり、新規治療につながりうる研究成果を継続していくことにより、将来的に国民の健康に大きく貢献できると考えている。
|
